Rheumatology, Osteoarthritis
12. May 2020
Characterization of the interleukin-17 Effect on Articular Cartilage in a Translational Model: An Explorative Study
Background: Osteoarthritis (OA) is a progressive, chronic disease characterized by articular cartilage destruction. The pro-inflammatory cytokine IL-17 levels have been reported elevated in serum and synovial fluid of OA patients and correlated with increased cartilage defects and bone remodeling. T…
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Journal:
Authors:
- Sinkeviciute D,
- Aspberg A,
- He Y,
- Bay-Jensen AC,
- Önnerfjord P,
Rheumatology, Osteoarthritis, Extracellular Matrix Research, Biomarker position
4. May 2020
Osteoarthritis: Current Molecular Biomarkers and the Way Forward
The ultimate hope of researchers and patients is a pathway to development of treatments for osteoarthritis to modify the disease process in addition to the symptoms. However, development of disease modifying drugs requires objective endpoints such as measures of joint structure, joint tissue homeost…
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Authors:
- Kraus VB,
- Karsdal MA,
Systemic Sclerosis, Rheumatology, Extracellular Matrix Research
28. Apr 2020
Type III, IV, and VI Collagens Turnover in Systemic Sclerosis - A Longitudinal Study
Tissue turnover, especially in the skin, is altered in systemic sclerosis (SSc), leading to tissue accumulation. The objective was to examine type III, IV, and VI collagens turnovers in SSc and investigate longitudinal alterations in relation to modified Rodnan Skin Score (mRSS). We included patient…
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Journal:
Authors:
- Juhl P,
- Bay-Jensen AC,
- Hesselstrand R,
- Siebuhr AS,
- Wuttge DM,
Rheumatology, Systemic Sclerosis, Respiratory System, Extracellular Matrix Research
23. Apr 2020
Correlation Between Serological Biomarkers of Extracellular Matrix Turnover and Lung Fibrosis and Pulmonary Artery Hypertension in Patients With Systemic Sclerosis
Objective: To determine the value of serological biomarkers of collagen degradation/turnover as serum markers of organ involvement in patients with systemic sclerosis (SSc).
Methods: Serum samples were obtained from 79 SSc patients and 19 healthy control subjects. Types I to VI collagen turnover,…
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Journal:
Authors:
- Kubo S,
- Siebuhr AS,
- Bay-Jensen AC,
- Juhl P,
- Karsdal MA,
- Satoh Y,
- Todoroki Y,
- Nakano K,
- Nakayamada S,
- Tanaka Y,
Rheumatology, Osteoarthritis, Extracellular Matrix Research
7. Apr 2020
Sprifermin (rhFGF18) Versus Vehicle Induces a Biphasic Process of Extracellular Matrix Remodeling in Human Knee OA Articular Cartilage Ex Vivo
Sprifermin, recombinant human fibroblast growth factor 18 (rhFGF18), induces cartilage regeneration in knees of patients with osteoarthritis (OA). We hypothesized that a temporal multiphasic process of extracellular matrix (ECM) degradation and formation underlie this effect. We aimed to characteriz…
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Journal:
Authors:
- Reker D,
- Siebuhr AS,
- Thudium CS,
- Gantzel T,
- Ladel C,
- Michaelis M,
- Aspberg A,
- Berchtold MW,
- Karsdal MA,
- Gigout A,
- Bay-Jensen AC,
Rheumatology, Osteoarthritis
15. Mar 2020
Clinical and Biochemical Factors Associated With Risk of Total Joint Replacement and Radiographic Progression in Osteoarthritis: Data From Two Phase III Clinical Trials
Objectives: Clinical trials of new disease-modifying treatments for osteoarthritis should demonstrate a positive effect on a functional outcome or reduction in joint failure in order to be considered successful. Total joint replacement (TJR) surgery may be considered as joint failure, but great vari…
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Journal:
Authors:
- Bihlet A,
- Bjerre-Bastos JJ,
- Andersen JR,
- Byrjalsen I,
- Karsdal MA,
- Bay-Jensen AC,
Rheumatology, Osteoarthritis, Extracellular Matrix Research
14. Nov 2019
Inflammation and joint destruction may be linked to the generation of cartilage metabolites of ADAMTS-5 through activation of toll-like receptors.
OBJECTIVE:
Links between pain and joint degradation are poorly understood. We investigated the role of activation of Toll-like receptors (TLR) by cartilage metabolites in initiating and maintaining the inflammatory loop in OA causing joint destruction.
METHODS:
Synovial membrane explants (SMEs)…
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Journal:
Authors:
- Sharma N,
- drobinski P,
- Kayed A,
- Chen Z,
- Kjelgaard-Petersen CF,
- Gantzel T,
- Karsdal MA,
- Michaels M,
- Ladel C,
- Bay-Jensen AC,
- Lindemann S,
- Thudium CS,
Rheumatology, Extracellular Matrix Research
3. Nov 2019
An Ex Vivo Tissue Culture Model of Cartilage Remodeling in Bovine Knee Explants.
Ex vivo culture systems cover a broad range of experiments dedicated to studying tissue and cellular function in a native setting. Cartilage is a unique tissue important for proper function of the synovial joint and is constituted by a dense extracellular matrix (ECM), rich in proteoglycan and type …
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Journal:
Authors:
- Thudium CS,
- Engstrom A,
- Groen SS,
- Karsdal MA,
- Bay-Jensen AC,
Rheumatology, Clinical Data Quality, Osteoarthritis
8. Oct 2019
Effect of Intra-Articular Sprifermin vs Placebo on Femorotibial Joint Cartilage Thickness in Patients With Osteoarthritis: The FORWARD Randomized Clinical Trial.
IMPORTANCE:
Sprifermin is under investigation as a disease-modifying osteoarthritis drug.
OBJECTIVE:
To evaluate the effects of sprifermin on changes in total femorotibial joint cartilage thickness in the more symptomatic knee of patients with osteoarthritis.
DESIGN, SETTING, AND PARTICIPANT…
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Journal:
Authors:
- Hochberg MC,
- Guermazi A,
- Guehring H,
- Aydemir A,
- Wax S,
- Fleuranceau-Morel P,
- Reinstrup Bihlet A,
- Byrjalsen I,
- Ragnar Andersen J,
- Eckstein F,
Rheumatology, Bone, Osteoporosis, Osteoarthritis, Biomarker position
30. Sep 2019
Biochemical markers in osteoarthritis with lessons learned from osteoporosis.
Osteoarthritis (OA) is a disease of the whole joint, including synovium, bone and cartilage. OA is a slow degenerative and very heterogeneous disease, with both varying levels of disease activity and progression. Biomarkers are urgently needed to assist drug developers in selecting and developing th…
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Authors:
Rheumatology, Osteoarthritis, Biomarker position, Bone
3. Sep 2019
Associations between biomarkers of bone and cartilage turnover, gender, pain categories and radiographic severity in knee osteoarthritis.
BACKGROUND:
Excessive cartilage degradation is a known characteristic of osteoarthritis (OA). Biochemical markers, such as uCTX-II, have been shown to be associated with disease severity, yet the tissue origin of CTX-II has been disputed. This analysis investigates the association between OA knee j…
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Journal:
Authors:
- Bihlet AR,
- Byrjalsen I,
- Bay-Jensen AC,
- Andersen JR,
- Christiansen C,
- Riis BJ,
- Karsdal MA,
Rheumatology, Spondyloarthropathies, Biomarker position
2. Aug 2019
Metabolites of type I, II, III, and IV collagen may serve as markers of disease activity in axial spondyloarthritis.
Local inflammation in axial spondyloarthritis (axSpA) leads to the release of collagen metabolites from the disease-affected tissue. We investigated whether collagen metabolites were associated with disease activity and could distinguish non-radiographic(nr)-axSpA from ankylosing spondylitis (AS). A…
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Journal:
Authors:
- Husakova M,
- Bay-Jensen AC,
- forejtová S,
- Zegzulkova K,
- Tomcik M,
- gregová M,
- Bubová K,
- Horínková J,
- Gatterová J,
- Pavelka K,
- Siebuhr AS,
Rheumatology, Osteoarthritis, Rheumatoid Arthritis
24. Jul 2019
Identification of pathological RA endotypes using blood-based biomarkers reflecting tissue metabolism. A retrospective and explorative analysis of two phase III RA studies.
There is an increasing demand for accurate endotyping of patients according to their pathogenesis to allow more targeted treatment. We explore a combination of blood-based joint tissue metabolites (neoepitopes) to enable patient clustering through distinct disease profiles. We analysed data from two…
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Journal:
Authors:
- Blair JPM,
- Bager C,
- Karsdal MA,
- Bay-Jensen AC,
Rheumatology, Osteoarthritis
26. Jun 2019
Incidence of total hip and total knee replacements from the prospective epidemiologic risk factor study: considerations for event driven clinical trial design
BACKGROUND:
Osteoarthritis (OA) leads to joint failure and total joint replacement (TJR, either hip (H) or knee (K)). Worsening of pain and joint space narrowing are believed to be surrogates for joint failure; however, we hypothesize that TJR, as a reflection of joint failure, can be used as an en…
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Authors:
Bone, Rheumatology, Osteoarthritis
5. Jun 2019
A dual amylin and calcitonin receptor agonist inhibits pain behavior and reduces cartilage pathology in an osteoarthritis rat model
OBJECTIVES:
Pain and disability are the main clinical manifestations of osteoarthritis, for which only symptomatic therapies are available. Hence, there is a need for therapies that can simultaneously alter disease progression and provide pain relief. KBP is a dual amylin- and calcitonin-receptor a…
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Journal:
Authors:
- Katri A,
- Dabrowska A,
- Lövfall H,
- Karsdal MA,
- Andreassen KV,
- Thudium CS,
- Henriksen K,
Rheumatology, Systemic Sclerosis
1. Mar 2019
Association of metabolites reflecting type III and VI collagen formation with modified Rodnan skin score in systemic sclerosis - a cross-sectional study
OBJECTIVE:
The objective was to investigate blood-based biomarkers of type I (PRO-C1), III (PRO-C3) and VI (PRO-C6) collagen formation in systemic sclerosis (SSc) patients and examine their correlation to modified Rodnan skin score (mRSS).
METHODS:
Limited (lSSc, n = 76) and diffuse SSc (dSSc, …
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Journal:
Authors:
- Juhl P,
- Vinderslev Iversen L,
- Karlsmark T,
- Karsdal MA,
- Bay-Jensen AC,
- Mogensen M,
- Siebuhr AS,
Rheumatology, Bone
28. Feb 2019
GPDPLQ1237-A Type II Collagen Neo-Epitope Biomarker of Osteoclast- and Inflammation-Derived Cartilage Degradation in vitro
C-telopeptide of type II collagen (CTX-II) has been shown to be a highly relevant biomarker of cartilage degradation in human rheumatic diseases, if measured in synovial fluid or urine. However, serum or plasma CTX-II have not been demonstrated to have any clinical utility to date. Here, we describe…
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Journal:
Authors:
- Löfvall H,
- Katri A,
- Dabrowska A,
- Karsdal MA,
- Luo Y,
- He Y,
- Manon-Jensen T,
- Dziegiel MH,
- Bay-Jensen AC,
- Thudium CS,
- Henriksen K,
Rheumatology, Rheumatoid Arthritis, Bone
22. Feb 2019
Combining Naproxen and a Dual Amylin and Calcitonin Receptor Agonist improves pain and structural outcomes in the Collagen-Induced Arthritis rat model
BACKGROUND:
Pain is a debilitating symptom of rheumatoid arthritis (RA), caused by joint inflammation and cartilage and bone destruction. Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to treat pain and inflammation in RA, but are not disease-modifying and do not prevent joint destruction w…
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Journal:
Authors:
- Katri A,
- Dabrowska A,
- Löfvall H,
- Ding M,
- Karsdal MA,
- Andreassen KV,
- Schneider Thudium C,
- Henriksen K,
Rheumatology, Spondyloarthropathies
11. Feb 2019
Metabolites of C-reactive protein and vimentin are associated with disease activity of axial spondyloarthritis.
OBJECTIVES:
Non-radiographic (nr-axSpA) and radiographic (AS) forms of axial spondyloarthritis (axSpA) share clinical features, but have different radiographic patterns. Radiographic progression is not associated with the current disease activity biomarkers. We investigated a matrix metalloproteina…
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Journal:
Authors:
- Siebuhr AS,
- Husakova M,
- forejtová S,
- Zegzulkova K,
- Tomcik M,
- Urbanova M,
- Grobelna K,
- Gatterova J,
- Bay-Jensen AC,
- Pavelka K,
Rheumatology, Osteoarthritis
31. Jan 2019
Molecular taxonomy of osteoarthritis for patient stratification, disease management and drug development
PURPOSE OF REVIEW:
This review focuses on the molecular taxonomy of osteoarthritis from the perspective of molecular biomarkers. We discuss how wet biochemical markers may be used to understand disease pathogenesis and progression and define molecular endotypes of osteoarthritis and how these corre…
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Journal:
Authors:
- mobasheri A,
- Van Spil WE,
- Budd E,
- Uzieliene I,
- Bernotiene E,
- Bay-Jensen AC,
- Larkin J,
- Levesque MC,
- Gualillo O,
- Henrotin Y,
Rheumatology, Osteoarthritis, Rheumatoid Arthritis
14. Jan 2019
Potential diagnostic value of a type X collagen neo-epitope biomarker for knee osteoarthritis.
OBJECTIVE:
Phenotypic changes of chondrocytes toward hypertrophy might be fundamental in the pathogenesis of OA, of which type X collagen (Col10) is a well-known marker. The purpose was to develop a specific immunoassay for blood quantification of a newly identified neo-epitope of type X collagen t…
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Journal:
Authors:
- He Y,
- Manon-Jensen T,
- Arendt-Nielsen L,
- Petersen KK,
- Christiansen T,
- Samuels J,
- Abramson S,
- Karsdal MA,
- Attur M,
- Bay-Jensen AC,
Rheumatology, Osteoarthritis
18. Dec 2018
Serological biomarker profiles of rapidly progressive osteoarthritis in tanezumab-treated patients.
There is a need for efficacious and safe pain treatments for OA (osteoarthritis). The nerve growth factor (NGF) antibody tanezumab is associated with high efficacy, but when combined with chronic NSAID treatment shows an increased risk of rapidly progressive osteoarthritis (RPOA) in a small group of…
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Journal:
Authors:
- Karsdal MA,
- Verburg KM,
- West CR,
- Bay-Jensen AC,
- Keller DS,
- Arends RHGP,
Rheumatology, Systemic Sclerosis, Extracellular Matrix Research
3. Dec 2018
Serum biomarkers of collagen turnover as potential diagnostic tools in diffuse systemic sclerosis: A cross-sectional study
BACKGROUND:
Systemic sclerosis (SSc) is characterized by excessive fibrosis throughout the body. This leads to the release of extracellular matrix (ECM) fragments into circulation, where they may be quantified as biomarkers. The objectives were to investigate levels of ECM turnover biomarkers and t…
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Journal:
Authors:
- Juhl P,
- Bay-Jensen AC,
- Karsdal MA,
- Siebuhr AS,
- Franchimont N,
- Chavez J,
Rheumatology, Extracellular Matrix Research, Systemic Sclerosis
20. Nov 2018
Citrullinated Vimentin and biglycan protein fingerprints as candidate serological biomarkers for disease activity in systemic sclerosis: A pilot study.
PURPOSE:
Extracellular matrix (ECM) deposition and remodelling in skin and lungs of systemic sclerosis (SSc) subjects lead to release of metabolites/biomarkers into circulation. We investigated if biomarkers of ECM degradation (biglycan and elastin) and macrophage activation (citrullinated vimentin…
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Journal:
Authors:
- Siebuhr AS,
- Juhl P,
- Bay-Jensen AC,
- Karsdal MA,
- Franchimont N,
- Chavez JC,
Rheumatology, Osteoarthritis
19. Nov 2018
Proposed study designs for approval based on a surrogate endpoint and a post-marketing study under FDA's accelerated approval regulations for disease modifying osteoarthritis drugs
In 1992, the Food and Drug Administration (FDA) instituted the accelerated approval regulations that allow drugs or biologics for serious conditions that fill an unmet medical need to be approved on the basis of a surrogate endpoint or an intermediate clinical endpoint. The current definition of a s…
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Journal:
Authors:
- Kraus VB,
- Simon LS,
- Katz JN,
- Neogi T,
- Hunter D,
- Guermazi A,
- Karsdal MA,
Rheumatology, Rheumatoid Arthritis
7. Nov 2018
The VICM biomarker is released from activated macrophages and inhibited by anti-GM-CSFRα-mAb treatment in rheumatoid arthritis patients.
OBJECTIVES:
Macrophages possess widespread pro-inflammatory, destructive, and remodelling capabilities that can critically contribute to acute and chronic diseases, such as rheumatoid arthritis (RA). Continuous monitoring and measurement of selective counteraction of macrophage activity in patients…
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Journal:
Authors:
- Mortensen JH,
- Guo X,
- De Los Reyes M,
- Dziegiel MH,
- Bay Jensen AC,
- White WI,
Rheumatology, Osteoarthritis
6. Nov 2018
A Novel High Sensitivity Type II Collagen Blood-Based Biomarker, PRO-C2, for Assessment of Cartilage Formation
N-terminal propeptide of type II collagen (PIINP) is a biomarker reflecting cartilage formation. PIINP exists in two main splice variants termed as type IIA and type IIB collagen NH₂-propeptide (PIIANP, PIIBNP). PIIANP has been widely recognized as a cartilage formation biomarker. However, the utili…
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Journal:
Authors:
- Luo Y,
- He Y,
- Gudmann NS,
- Henriksen K,
- Simonsen O,
- Ladel C,
- Michaels M,
- Mobasheri A,
- Karsdal MA,
- Bay-Jensen AC,
Rheumatology, Osteoarthritis
7. Sep 2018
IL-37 diminishes proteoglycan loiss in human OA cartilage: donor-specific link between IL-37 and MMP-3.
OBJECTIVE:
A hallmark of osteoarthritis (OA) is degradation of articular cartilage proteoglycans. In isolated human OA chondrocytes, the anti-inflammatory cytokine Interleukin-37 (IL-37) lowers the expression of the proteolytic MMP and ADAMTS enzymes, which mediate this degradation. Therefore, we i…
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Journal:
Authors:
- Van Geffen EW,
- Van Caam APM,
- Van de Loo FA,
- Van Lent PLEM,
- Koenders MI,
- Thudium CS,
- Bay-Jensen AC,
- Blaney Davidson EN,
- Van der Kraan PM,
Rheumatology, Osteoarthritis
29. Jul 2018
Tofacitinib and TPCA-1 Exert Chondroprotective Effects on Extracellular Matrix Turnover in Bovine Articular Cartilage Ex vivo.
OBJECTIVE:
Currently, there are no disease-modifying osteoarthritis drugs (DMOADs) approved for osteoarthritis. It is hypothesized that a subtype of OA may be driven by inflammation and may benefit from treatment with anti-inflammatory small molecule inhibitors adopted from treatments of rheumatoid…
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Journal:
Authors:
- Kjelgaard-Petersen CF,
- Sharma N,
- Kayed A,
- Karsdal MA,
- Mobasheri A,
- Hägglund P,
- Bay-Jensen AC,
- Thudium CS,
Rheumatology, Spondyloarthropathies
14. May 2018
Is radiographic progression in radiographic axial spondyloarthritis related to matrix metalloproteinase degradation of extracellular matrix?
BACKGROUND:
Radiographic axial spondyloarthritis (r-axSpA) is associated with extracellular matrix (ECM) remodelling of affected tissues. We investigated whether there was a relationship between biomarkers of ECM remodelling and 2-year radiographic progression in r-axSpA.
METHODS:
Patients from…
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Journal:
Authors:
- Siebuhr AS,
- van de Heijde D,
- Bay-Jensen AC,
- Karsdal MA,
- Landewé R,
- van Tubergen A,
- Ramiro S,
Rheumatology, Rheumatoid Arthritis
8. May 2018
Type IV collagen metabolism is associated with disease activity, radiographic progression and response to tocilizumab in rheumatoid arthritis
OBJECTIVES:
The expanding spectrum of targeted therapies for rheumatoid arthritis (RA) implies a need for development of precision tools for disease assessment reflecting pathobiologic processes. Type IV collagen is an abundant protein of basement membranes, but is also present in the intercellular…
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Journal:
Authors:
- Gudmann NS,
- Junker P,
- Juhl P,
- Thudium CS,
- Siebuhr AS,
- Byrjalsen I,
- Karsdal MA,
- Bay-Jensen AC,
Rheumatology, Osteoarthritis
25. Apr 2018
Protein biomarkers associated with pain mechanisms in osteoarthritis
Osteoarthritis (OA) is the most common arthritic disease in the world, leading to debilitating pain and destruction of joint tissues. While pain is the hallmark symptom of osteoarthritis, clear associations between pain and disease processes involved in joint deterioration are lacking. OA pain is mu…
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Journal:
Authors:
- Thudium CS,
- Löfvall H,
- Karsdal MA,
- Bay-Jensen AC,
- Bihlet A,
Rheumatology, Osteoarthritis, Extracellular Matrix Research
25. Apr 2018
Aggrecanase degradation of type III collagen is associated with clinical knee pain
There is a lack of biochemical markers for non-invasive and objective assessment of symptomatic osteoarthritis (OA). Aggrecanase activity has been shown to be associated with joint deterioration and symptomatic disease through the degradation of extracellular matrix proteins, such as type III collag…
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Journal:
Authors:
- Bay-Jensen AC,
- Kjelgaard-Petersen CF,
- Petersen KK,
- Arendt-Nielsen L,
- Quasnichka HL,
- Mobasheri A,
- Karsdal MA,
- Leeming DJ,
Rheumatology, Rheumatoid Arthritis
18. Apr 2018
Translational Biomarkers and Ex Vivo Models of Joint Tissues as a Tool for Drug Development in Rheumatoid Arthritis
OBJECTIVE:
Rheumatoid arthritis (RA) is a chronic, autoimmune and degenerative joint disease leading to disability, reduced life quality, and increased mortality. Although several synthetic and biological disease modifying anti-rheumatic drugs (DMARDs) are available, there is still a medical need f…
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Journal:
Authors:
- Kjelgaard-Petersen CF,
- Platt A,
- Braddock M,
- Jenkins MA,
- Musa K,
- Graham E,
- Gantzel T,
- Slynn G,
- Weinblatt ME,
- Karsdal MA,
- Thudium CS,
- Bay-Jensen AC,
Bone, Extracellular Matrix Research, Osteoarthritis
10. Apr 2018
Osteoclasts degrade bone and cartilage knee joint compartments through different resorption processes
BACKGROUND:
Osteoclasts have been strongly implicated in osteoarthritic cartilage degradation, at least indirectly via bone resorption, and have been shown to degrade cartilage in vitro. The osteoclast resorption processes required to degrade subchondral bone and cartilage-the remodeling of which i…
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Journal:
Authors:
- Löfvall H,
- Newbould H,
- Karsdal MA,
- Dziegiel MH,
- Richter J,
- Henriksen K,
- Thudium CS,
Extracellular Matrix Research, Systemic Sclerosis, Rheumatology, Chronic Obstructive Pulmonary Disease
1. Mar 2018
Development of a Neo-Epitope Specific Assay for Serological Assessment of Type VII Collagen Turnover and Its Relevance in Fibroproliferative Disorders
Type VII collagen is the main component of the anchoring fibrils connecting the basement membrane to the underlying interstitial matrix. Mutations in the type VII collagen gene cause dystrophic epidermolysis bullosa. Increased levels of type VII collagen in the skin have been reported in patients wi…
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Journal:
Authors:
- Sand JMB,
- Lamy P,
- Juhl P,
- Siebuhr AS,
- Iversen LV,
- Nawrocki A,
- Larsen MR,
- Domsic RT,
- Franchimont N,
- Chavez J,
- Karsdal MA,
- Leeming DJ,
Rheumatology, Rheumatoid Arthritis
14. Feb 2018
Increased remodelling of interstitial collagens and basement membrane is suppressed by treatment in patients with rheumatoid arthritis: serological evaluation of a one-year prospective study of 149 Japanese patients
OBJECTIVES:
This prospective study aimed to use serological biomarkers for evaluation of, connective tissue turnover, in a population of 149 Japanese patients with rheumatoid arthritis (RA). It was aimed to investigate how the connective tissue was affected by treatment at follow-up after 1 year (+…
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Journal:
Authors:
- Gudmann NS,
- Hirata S,
- Karsdal MA,
- Kubo S,
- Bay-Jensen AC,
- Tanaka Y,
Rheumatology, Rheumatoid Arthritis
31. Jan 2018
IL-6 receptor inhibition modulates type III collagen and C-reactive protein degradation in rheumatoid arthritis patients with an inadequate response to anti-tumour necrosis factor therapy: analysis of connective tissue turnover in the tocilizumab RADIATE.
OBJECTIVES:
The objective of this study was to examine the tissue degradation in response to anti-IL6 receptor treatment in rheumatoid arthritis (RA) patients which are anti-TNF-α inadequate responders.
METHODS:
RADIATE was a randomised, double-blinded, placebo-controlled, parallel-group, phase…
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Journal:
Authors:
- Juhl P,
- Thudium CS,
- Gudmann NS,
- Karsdal MA,
- Bay-Jensen AC,
- Siebuhr AS,
Osteoarthritis
17. Jan 2018
Identification of pain categories associated with change in pain in patients receiving placebo: Data from Two Phase 3 Randomized Clinical Trials in Symptomatic Knee Osteoarthritis
BACKGROUND:
Pain is the principal clinical symptom of osteoarthritis (OA), and development of safe and effective analgesics for OA pain is needed. Drug development of new analgesics for OA pain is impaired by substantial change in pain in patients receiving placebo, and more data describing clinica…
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Journal:
Authors:
- Bihlet AR,
- Byrjalsen I,
- Bay-Jensen AC,
- Andersen JR,
- Christiansen C,
- Riis BJ,
- Valter I,
- Karsdal MA,
- Hochberg MC,
Rheumatology, Osteoarthritis, Clinical Data Quality
9. Jan 2018
Gender Differences in Knee Joint Congruity Quantified from MRI: A Validation Study with Data from Center for Clinical and Basic Research and Osteoarthritis Initiative.
Objective Gender is a risk factor in the onset of osteoarthritis (OA). The aim of the study was to investigate gender differences in contact area (CA) and congruity index (CI) in the medial tibiofemoral (MTF) joint in 2 different cohorts, quantified automatically from magnetic resonance imaging (MRI…
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Journal:
Authors:
- Tummala S,
- Schipdor D,
- Byrjalsen I,
- Dam EB,
Rheumatology, Osteoarthritis
12. Dec 2017
Sprifermin (rhFGF18) Modulates Extracellular Matrix Turnover in Cartilage Explants ex vivo
BACKGROUND:
Sprifermin (recombinant human fibroblast growth factor 18) is in clinical development as a potential disease-modifying osteoarthritis drug (DMOAD). In vitro studies have shown that cartilage regenerative properties of sprifermin involve chondrocyte proliferation and extracellular matrix…
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Journal:
Authors:
- Reker D,
- Kjelgaard-Petersen CF,
- Siebuhr AS,
- Michaelis M,
- Gigout A,
- Karsdal MA,
- Ladel C,
- Bay-Jensen AC,
Rheumatology, Rheumatoid Arthritis
23. Oct 2017
Blockade of GM-CSF pathway induced sustained suppression of myeloid and T cell activities in rheumatoid arthritis
OBJECTIVES:
Targeting the granulocyte-macrophage colony-stimulating factor (GM-CSF) pathway holds great potential in the treatment of inflammatory diseases. Mavrilimumab, a human monoclonal GM-CSF receptor-α antibody, has demonstrated clinical efficacy in RA. Our current study aimed to elucidate me…
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Journal:
Authors:
- Guo X,
- Higgs BW,
- Bay-Jensen AC,
- Wu Y,
- Karsdal MA,
- Kuziora M,
- Godwood A,
- Close D,
- Ryan PC,
- Roskos LK,
- White WI,
Rheumatology, Osteoarthritis
16. Oct 2017
Development and use of biochemical markers in osteoarthritis: current update
PURPOSE OF REVIEW:
There is an increasing demand for noninvasive and descriptive biochemical markers (biomarkers) in osteoarthritis; for enabling early drug development (including translational research), evaluating clinical trial at an early stage and for subtyping. Purpose of the review is to rev…
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Journal:
Authors:
- Bay-Jensen AC,
- Thudium CS,
- Mobasheri A,
Rheumatology, Osteoarthritis
14. Oct 2017
Biochemical marker discovery, testing and evaluation for facilitating OA drug discovery and development
Osteoarthritis (OA) is the most common form of joint disease. This presents the OA research community and pharmaceutical companies developing disease-modifying OA drugs (DMOADs) with great opportunities. The different OA subtypes complicate the traditional approaches for developing new treatments. I…
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Journal:
Authors:
- Bay-Jensen AC,
- Thudium CS,
- Mobasheri A,
- Gualillo O,
Rheumatology, Osteoarthritis
28. Sep 2017
Safety, Tolerability, and Pharmacodynamics of an Anti-Interleukin-1 α/β Dual Variable Domain Immunoglobulin in Patients With Osteoarthritis of the Knee: A Randomized Phase 1 Study
OBJECTIVE:
To investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of ABT-981, a human dual variable domain immunoglobulin simultaneously targeting interleukin (IL)-1α and IL-1β, in patients with knee osteoarthritis (OA).
METHOD:
This was a randomized, double-blind, plac…
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Journal:
Authors:
- Wang SX,
- Abramson SB,
- Attur M,
- Karsdal MA,
- Preston RA,
- Lozada CJ,
- Kosloski MP,
- Hong F,
- Jiang P,
- Saltarelli MJ,
- Hendrickson BA,
- Medema JK,
Rheumatology, Osteoarthritis
16. Sep 2017
Biomarkers for equine joint injury and osteoarthritis
We report the results of a symposium aimed at identifying validated biomarkers that can be used to complement clinical observations for diagnosis and prognosis of joint injury leading to equine osteoarthritis (OA). Biomarkers might also predict pre-fracture change that could lead to catastrophic bon…
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Journal:
Authors:
- McIlwraith CW,
- Kawcak CE,
- Frisbie DD,
- Little CB,
- Clegg PD,
- Peffers MJ,
- Karsdal MA,
- Ekman S,
- Laverty S,
- Slayden RA,
- Sandell LJ,
- Lohmander LS,
- Kraus VB,
Rheumatology, Osteoarthritis, Obesity
9. Sep 2017
A machine learning approach for the identification of new biomarkers for knee osteoarthritis development in overweight and obese women
OBJECTIVE:
Knee osteoarthritis (OA) is among the higher contributors to global disability. Despite its high prevalence, currently, there is no cure for this disease. Furthermore, the available diagnostic approaches have large precision errors and low sensitivity. Therefore, there is a need for new …
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Journal:
Authors:
- Bacardit J,
- Henrotin Y,
- Bierma-Zeinstra SMA,
- Thudium CS,
- Bay-Jensen AC,
- Runhaar J,
- Lazzarini N,
Rheumatology, Extracellular Matrix Research
30. Aug 2017
Changes of patient-reported outcomes and protein fingerprint biomarkers after exercise therapy for axial spondyloarthritis
The objective of this study was to investigate the patient-reported outcomes (PROs) and matrix metalloproteinase (MMP) derived extracellular matrix (ECM) biomarkers in non-radiographic (nr)-axial spondyloarthritis (axSpA) and radiographic (r)-axSpA after exercise intervention. Forty-six axSpA patien…
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Journal:
Authors:
- Husakova M,
- Siebuhr AS,
- Pavelka K,
- Spiritovic M,
- Bay-Jensen AC,
- Levitova A,
Rheumatology, Rheumatoid Arthritis
28. Aug 2017
Suppression of active, but not total MMP-3, is associated with treatment response in a phase III clinical study of rheumatoid arthritis
OBJECTIVE:
Biologics for rheumatoid arthritis (RA) patients with moderate to severe disease may preserve joint function. Matrix metalloproteinase 3 (MMP-3), a key tissue degrading protease, is highly elevated in RA. MMP-3, which measures the total pool of circulating MMP-3 species (cMMP3), is a com…
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Journal:
Authors:
- Siebuhr AS,
- Kjelgaard-Petersen CF,
- Sun S,
- Byrjalsen I,
- Christiansen C,
- Karsdal MA,
- Bay-Jensen AC,
Rheumatology, Osteoarthritis
18. Aug 2017
Sprifermin (rhFGF18) enables proliferation of chondrocytes producing a hyaline cartilage matrix
OBJECTIVE:
Fibroblast growth factor (FGF) 18 has been shown to increase cartilage volume when injected intra-articularly in animal models of osteoarthritis (OA) and in patients with knee OA (during clinical development of the recombinant human FGF18, sprifermin). However, the exact nature of this e…
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Journal:
Authors:
- Gigout A,
- Guehring H,
- Froemel D,
- Meurer A,
- Ladel C,
- Reker D,
- Bay-Jensen AC,
- Karsdal MA,
- Lindemann S,
Obesity, Rheumatology, Osteoarthritis
27. Jul 2017
Effects of dietary weight loss with and without exercise on interstitial matrix turnover and tissue inflammation biomarkers in adults with knee osteoarthritis: the Intensive Diet and Exercise for Arthritis trial (IDEA)
OBJECTIVE:
To examine the effects of dietary weight loss, with and without exercise, on selected soluble biomarkers in overweight and obese older adults with symptomatic knee osteoarthritis (OA).
DESIGN:
Blood samples were analyzed from 429 participants in the Intensive Diet and Exercise for Ar…
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Journal:
Authors:
- Loeser RF,
- Beavers DP,
- Bay-Jensen AC,
- Karsdal MA,
- Nicklas BJ,
- Guermazi A,
- Hunter DJ,
- Messier SP,
Rheumatology, Hematology, Hemophilia
24. Apr 2017
Serological biomarkers detect active joint destruction and inflammation in patients with haemophilic arthropathy
INTRODUCTION:
Progressive arthropathy caused by recurrent joint bleeds is a severe complication in haemophilia.
AIM:
We investigated whether biomarkers of cartilage and bone degradation, and inflammation were altered in haemophilia patients and whether these biomarkers could identify haemophili…
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Journal:
Authors:
- Hua B,
- Olsen EHN,
- Sun S,
- Gudme CN,
- Wang L,
- Vandahl B,
- Roepstorff K,
- Kjelgaard-Hansen M,
- Sørensen BB,
- Zhao Y,
- Karsdal MA,
- Manon-Jensen T,
Extracellular Matrix Research, Osteoarthritis
22. Mar 2017
Biomarker of extracellular matrix remodelling C1M and proinflammatory cytokine IL-6 are related to synovitis and pain in endstage knee osteoarthritis patients
Little is known about local and systemic biomarkers in relation to synovitis and pain in end-stage osteoarthritis (OA) patients. We investigated the associations between the novel extracellular matrix biomarker, C1M, and local and systemic interleukin 6 (IL-6) with synovitis and pain. Serum C1M, pla…
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Journal:
Authors:
- Radojcic MR,
- Thudium CS,
- Henriksen K,
- Tan K,
- Karlsten R,
- Dudley A,
- Chessell I,
- Karsdal MA,
- Bay-Jensen AC,
- Arbit E,
- Guermazi A,
Osteoarthritis, Rheumatology, Extracellular Matrix Research
20. Feb 2017
Chondrocyte secretome: a source of novel insights and exploratory biomarkers of osteoarthritis
The extracellular matrix (ECM) of articular cartilage is comprised of complex networks of proteins and glycoproteins, all of which are expressed by its resident cell, the chondrocyte. Cartilage is a unique tissue given its complexity and ability to resist repeated load and deformation. The mechanism…
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Journal:
Authors:
- Sanchez C,
- Bay-Jensen AC,
- Pap T,
- Dvir-Ginzberg M,
- Quasnichka H,
- Barrett-Jolley R,
- Mobasheri A,
- Henrotin Y,
Rheumatoid Arthritis, Rheumatology, Extracellular Matrix Research
17. Feb 2017
The minor collagens in articular cartilage
Articular cartilage is a connective tissue consisting of a specialized extracellular matrix (ECM) that dominates the bulk of its wet and dry weight. Type II collagen and aggrecan are the main ECM proteins in cartilage. However, little attention has been paid to less abundant molecular components, es…
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Journal:
Authors:
- Luo Y,
- Sinkeviciute D,
- He Y,
- Karsdal MA,
- Henrotin Y,
- Mobasheri A,
- Önnerfjord P,
- Bay-Jensen AC,
Osteoarthritis
20. Jan 2017
Identification of serological biomarker profiles associated with total joint replacement in osteoarthritis patients
OBJECTIVE:
Establish a biomarker panel associated with all-cause total joint replacement (TJR) through identification of patients with osteoarthritis (OA) who do or do not progress to TJR and investigate effects of nonsteroidal anti-inflammatory drugs (NSAIDs).
DESIGN:
Serum samples from patien…
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Journal:
Authors:
- Arends RH,
- Karsdal MA,
- Verburg KM,
- West CR,
- Bay-Jensen AC,
- Keller DS,
Rheumatology, Osteoarthritis
16. Jan 2017
Osteoarthritis Year in Review 2016: biomarkers (biochemical markers)
PURPOSE:
The aim of this "Year in Review" article is to summarize and discuss the implications of biochemical marker related articles published between the Osteoarthritis Research Society International (OARSI) 2015 Congress in Seattle and the OARSI 2016 Congress in Amsterdam.
METHODS:
The PubMe…
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Journal:
Authors:
- Mobasheri A,
- Bay-Jensen AC,
- Van Spil WE,
- Larkin J,
- Levesque MC,
Rheumatology
5. Jan 2017
Type I and III collagen turnover is increased in axial spondyloarthritis and psoriatic arthritis. Associations with disease activity and diagnostic capacity
OBJECTIVES:
To investigate the turnover of type I and III collagen by neo-epitope markers in patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA).
METHODS:
Patients with PsA (n=101) or axSpA (n=110) and healthy subjects (n=120) were included. Demographic and clinical data…
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Journal:
Authors:
- Gudmann NS,
- Siebuhr AS,
- Christensen AF,
- Ejstrup L,
- Sørensen GL,
- Loft AG,
- Karsdal MA,
- Bay-Jensen AC,
- Munk HL,
- Junker P,
Rheumatology, Osteoarthritis
11. Oct 2016
The association between histological, macroscopic and magnetic resonance imaging assessed synovitis in end-stage knee osteoarthritis: a cross-sectional study
OBJECTIVES:
To investigate the association between magnetic resonance imaging (MRI), macroscopic and histological assessments of synovitis in end-stage knee osteoarthritis (KOA).
METHODS:
Synovitis of end-stage osteoarthritic knees was assessed using non-contrast-enhanced (CE), contrast-enhance…
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Journal:
Authors:
- Riis RG,
- Gudbergsen H,
- Simonsen O,
- Henriksen M,
- Al-Mashkur N,
- Eld M,
- Petersen KK,
- Kubassova O,
- Bay Jensen AC,
- Damm J,
- Bliddal H,
- Arendt-Nielsen L,
- Boesen MP,
Rheumatology, Osteoarthritis
2. Aug 2016
Disease-modifying treatments for osteoarthritis (DMOADs) of the knee and hip: lessons learned from failures and opportunities for the future
Osteoarthritis (OA) is the biggest unmet medical need among the many musculoskeletal conditions and the most common form of arthritis. It is a major cause of disability and impaired quality of life in the elderly. We review several ambitious but failed attempts to develop joint structure-modifying t…
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Journal:
Authors:
- Karsdal MA,
- Michaelis M,
- Ladel C,
- Siebuhr AS,
- Bihlet AR,
- Andersen JR,
- Guehring H,
- Christiansen C,
- Bay-Jensen AC,
- Kraus VB,
Rheumatology
16. Jun 2016
Chondrocyte activity is increased in psoriatic arthritis and axial spondyloarthritis
BACKGROUND:
Psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) are chronic inflammatory rheumatic diseases with complex origins. Both are characterized by altered extracellular matrix remodeling in joints and entheses that results in destructive and osteochondral proliferative lesions. T…
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Journal:
Authors:
- Gudmann NS,
- Munk HL,
- Christensen AF,
- Ejstrup L,
- Sørensen GL,
- Loft AG,
- Karsdal MA,
- Bay-Jensen AC,
- He Y,
- Siebuhr AS,
- Junker P,
Rheumatology
2. Jun 2016
Intercritical circulating levels of neo-epitopes reflecting matrixmetalloprotease-driven degradation as markers of gout and frequent gout attacks
OBJECTIVE:
Recurrent flares constitute the main clinical burden of gout. Our aim was to assess whether biomarkers measuring MMP tissue degradation could be used as markers of frequent gout flares.
METHODS:
Fasting plasma samples from 112 men with gout and 170 controls, along with serum samples …
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Journal:
Authors:
- Valdes AM,
- Manon-Jensen T,
- Abhishek A,
- Jenkins W,
- Siebuhr AS,
- Karsdal MA,
- Doherty S,
- Zhang W,
- Richardson H,
- Doherty M,
- Bay-Jensen AC,
Rheumatology, Osteoarthritis
5. May 2016
The Need for Predictive, Prognostic, Objective and Complementary Blood-Based Biomarkers in Osteoarthritis (OA)
Osteoarthritis (OA) has traditionally been viewed as a non-inflammatory arthropathy and has not been considered a ‘serious disease’. However, this view has radically changed in recent years, due to the complexity and heterogeneity of the patient populations, spiralling socio-economical costs and lon…
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Journal:
Authors:
- Bay-Jensen AC,
- Henrotin Y,
- Karsdal MA,
- Mobasheri A,
Rheumatology, Osteoarthritis
28. Apr 2016
Osteoarthritis biomarkers derived from cartilage extracellular matrix: Current status and future perspectives
Specific soluble biomarkers can be powerful tools for the diagnosis, prognosis and personalized management of osteoarthritis (OA). Biomarkers are potential indicators of the effect of a drug on cartilage metabolism and provide crucial information about the mechanisms of drug action. In this review, …
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Journal:
Authors:
- Henrotin Y,
- Sanchez C,
- Bay-Jensen AC,
- Mobasheri A,
Rheumatology, Osteoarthritis
1. Apr 2016
Association between biomarkers of tissue inflammation and progression of osteoarthritis: evidence from the Rotterdam study cohort
BACKGROUND:
We aimed to investigate the prognostic value of two biomarkers of tissue inflammation, matrix metalloproteinase-dependent degradation of C-reactive protein (CRPM) and connective tissue type I collagen turnover (C1M), on the incidence and progression of radiographic osteoarthritis (OA) i…
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Journal:
Authors:
- Saberi Hosnijeh F,
- Siebuhr AS,
- Uitterlinden AG,
- Oei EH,
- Hofman A,
- Karsdal MA,
- Bierma-Zeinstra SM,
- Bay-Jensen AC,
- van Meurs JB,
Rheumatology, Rheumatoid Arthritis
28. Mar 2016
Neo-Epitopes-Fragments of Cartilage and Connective Tissue Degradation in Early Rheumatoid Arthritis and Unclassified Arthritis
OBJECTIVE:
Tissue destruction in rheumatoid arthritis (RA) is predominantly mediated by matrix metalloproteinases (MMPs), thereby generating protein fragments. Previous studies have revealed that these fragments include MMP-mediated collagen type I, II, and III degradation, citrullinated and MMP-de…
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Journal:
Authors:
- Maijer KI,
- Gudmann NS,
- Karsdal MA,
- Gerlag DM,
- Tak PP,
- Bay-Jensen AC,
Rheumatology, Spondyloarthropathies
10. Feb 2016
CRP and a biomarker of type I collagen degradation, C1M, can differentiate anti-inflammatory treatment response in ankylosing spondylitis
AIM:
To investigate if tissue turnover biomarkers were efficacy biomarkers in ankylosing spondylitis and if the biomarkers at baseline predicted a good outcome (BASDAI50).
PATIENTS & METHODS:
Twenty-two etanercept treated ankylosing spondylitis patients were investigated for inflammation (CRP, …
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Journal:
Authors:
- Siebuhr AS,
- Bay-Jensen AC,
- Karsdal MA,
- Lories RJ,
- de Vlam K,
Rheumatology, Osteoarthritis, Extracellular Matrix Research
10. Feb 2016
Synovitis biomarkers: ex vivo characterization of three biomarkers for identification of inflammatory osteoarthritis
OBJECTIVE:
Characterize biomarkers measuring extracellular matrix turnover of inflamed osteoarthritis synovium.
METHODS:
Human primary fibroblast-like synoviocytes and synovial membrane explants (SMEs) treated with various cytokines and growth factors were assessed by C1M, C3M, and acMMP3 in …
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Journal:
Authors:
- Bay-Jensen AC,
- Karsdal MA,
- Ladel C,
- Christiansen TG,
- Siebuhr AS,
- Kjelgaard-Petersen CF,
Rheumatology, Osteoarthritis
25. Jan 2016
Osteoarthritis year in review 2015: soluble biomarkers and the BIPED criteria
OBJECTIVE:
To review and summarize biomarker data published from April 2014 to May 2015 to provide insight to the ongoing work in the field of osteoarthritis (OA). Furthermore, to summarize the BIPED criteria and set it in context of the medical needs of 2015.
METHODS:
PubMed was used as search…
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Journal:
Authors:
- Bay-Jensen AC,
- Reker D,
- Kjelgaard-Petersen CF,
- Mobasheri A,
- Karsdal MA,
- Ladel C,
- Henrotin Y,
- Thudium CS,
Rheumatology, Rheumatoid Arthritis
20. Jan 2016
Early changes in blood-based joint tissue destruction biomarkers are predictive of response to tocilizumab in the LITHE study
BACKGROUND:
Rheumatoid arthritis (RA) is characterized by gradual joint destruction. Tocilizumab (TCZ) significantly suppresses symptoms, however not all patients are protected from joint damage. We investigated whether early measurement of specific biomarkers could predict early joint protection r…
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Journal:
Authors:
- Bay-Jensen AC,
- Platt A,
- Siebuhr AS,
- Christiansen C,
- Byrjalsen I,
- Karsdal MA,
Rheumatology, Osteoarthritis
21. Dec 2015
Serum cartilage oligomeric matrix protein and development of radiographic and painful knee osteoarthritis. A community-based cohort of middle-aged women
CONTEXT AND OBJECTIVE:
We evaluated the predictive value of serum cartilage oligomeric matrix protein (sCOMP) levels over 20 years on the development of radiographic (RKOA) and painful knee osteoarthritis (KOA) in a longitudinal cohort of middle-aged women.
MATERIALS AND METHODS:
Five hundred a…
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Journal:
Authors:
- Kluzek S,
- Bay-Jensen AC,
- Judge A,
- Karsdal MA,
- Shorthose M,
- Spector T,
- Hart D,
- Newton JL,
- Arden NK,
Rheumatology, Osteoarthritis
2. Dec 2015
Sensitization and Serological Biomarkers in Knee Osteoarthritis Patients With Different Degrees of Synovitis
OBJECTIVE:
Synovitis is a frequent condition in knee osteoarthritis (KOA) and has been associated with pain. This study investigated the links between the pressure hyperalgesia, the clinical pain, the degree of the synovitis, inflammatory biomarkers, and tissue-specific biomarkers in KOA patients.
…
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Journal:
Authors:
- Petersen KK,
- Siebuhr AS,
- Graven-Nielsen T,
- Simonsen O,
- Boesen MP,
- Gudbergsen H,
- Karsdal MA,
- Bay-Jensen AC,
- Arendt-Nielsen L,
Rheumatology, Osteoarthritis
20. Oct 2015
Inflammation (or synovitis)-driven osteoarthritis: an opportunity for personalizing prognosis and treatment?
The disabling and painful disease osteoarthritis (OA) is the most common form of arthritis. Strong evidence suggests that a subpopulation of OA patients has a form of OA driven by inflammation. Consequently, understanding when inflammation is the driver of disease progression and which OA patients m…
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Journal:
Authors:
- Siebuhr AS,
- Bay-Jensen AC,
- Jordan JM,
- Kjelgaard-Petersen CF,
- Christiansen C,
- Abramson SB,
- Attur M,
- Berenbaum F,
- Kraus V,
- Karsdal MA,
Rheumatology, Systemic Sclerosis
1. Oct 2015
Suppression of T Cell Activation and Collagen Accumulation by an Anti-IFNAR1 mAb, Anifrolumab, in Adult Patients with Systemic Sclerosis
Type I IFNs are implicated in the pathophysiology of systemic sclerosis (SSc). Recently, a Phase I open-label trial was conducted with an anti-IFNAR1 receptor antibody (anifrolumab) in adult SSc patients. In this study, we aim to assess the downstream effects of anifrolumab and elucidate the role of…
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Journal:
Authors:
- Guo X,
- Higgs BW,
- Bay-Jensen AC,
- Karsdal MA,
- Yao Y,
- Roskos LK,
- White WI,
Rheumatology, Osteoarthritis
1. Aug 2015
Call for standardized definitions of osteoarthritis and risk stratification for clinical trials and clinical use
Osteoarthritis (OA) is a heterogeneous disorder. The goals of this review are (1) To stimulate use of standardized nomenclature for OA that could serve as building blocks for describing OA and defining OA phenotypes, in short to provide unifying disease concepts for a heterogeneous disorder; and (2)…
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Journal:
Authors:
- Kraus VB,
- Blanco FJ,
- Englund M,
- Karsdal MA,
- Lohmander LS,
Rheumatology, Osteoarthritis
24. Apr 2015
The effect of protease inhibitors on the induction of osteoarthritis-related biomarkers in bovine full-depth cartilage explants
OBJECTIVE:
The specific degradation of type II collagen and aggrecan by matrix metalloproteinase (MMP)-9, -13 and ADAMTS-4 and -5 (aggrecanase-1 and -2) in the cartilage matrix is a critical step in pathology of osteoarthritis (OA). The aims of this study were: i) To investigate the relative contri…
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Journal:
Authors:
- He Y,
- Zheng Q,
- Jiang M,
- Christiansen TG,
- Kassem M,
- Karsdal MA,
- Bay-Jensen AC,
Rheumatology, Osteoarthritis
1. Apr 2015
OA phenotypes, rather than disease stage, drive structural progression--identification of structural progressors from 2 phase III randomized clinical studies with symptomatic knee OA
BACKGROUND/PURPOSE:
The aim of this study was to identify key characteristics of disease progression through investigation of the association of radiographic progression over two years with baseline Joint Space Width (JSW), Kellgren-Lawrence (KL) grade, Western Ontario and McMaster Universities Art…
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Journal:
Authors:
- Karsdal MA,
- Bihlet A,
- Byrjalsen I,
- Alexandersen P,
- Ladel C,
- Michaels M,
- Andersen JR,
- Riis BJ,
- Kraus V,
- Bay-Jensen AC,
- Christiansen C,
Rheumatology, Osteoarthritis
1. Apr 2015
Treatment of symptomatic knee osteoarthritis with oral salmon calcitonin: results from two phase 3 trials
PURPOSE:
To evaluate the structure-modifying and symptom efficacy, as well as safety and tolerability of oral salmon calcitonin (sCT) formulated with a 5-CNAC carrier (a molecule based on Eligen(®) technology), in osteoarthritis (OA) patients with moderate to severe knee pain and joint structural d…
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Journal:
Authors:
- Karsdal MA,
- Byrjalsen I,
- Alexandersen P,
- Bihlet A,
- Andersen JR,
- Riis BJ,
- Bay-Jensen AC,
- Christiansen C,
- CSMC021C2301/1 investigators,
Rheumatology, Alkaptonuria
1. Mar 2015
Twelve novel HGD gene variants identified in 99 alkaptonuria patients: focus on 'black bone disease' in Italy
Alkaptonuria (AKU) is an autosomal recessive disorder caused by mutations in homogentisate-1,2-dioxygenase (HGD) gene leading to the deficiency of HGD enzyme activity. The DevelopAKUre project is underway to test nitisinone as a specific treatment to counteract this derangement of the phenylalanine-…
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Journal:
Authors:
- Nemethova M,
- Radvanszky J,
- Kadasi L,
- Ascher DB,
- Pires DE,
- Blundell TL,
- Porfirio B,
- Mannoni A,
- Santucci A,
- Milucci L,
- Sestini S,
- , Biolcati G,
- Sorge,
- Aurizi C,
- Aquaron R,
- Alsbou M,
- Marques Lourenço C,
- Ramadevi K,
- Ranganath LR,
- Gallagher JA,
- van Kan C,
- Hall AK,
- Olsson B,
- Ayoob H,
- Timmis OG,
- Le Quan Sang KH,
- Genovese F,
- Imrich R,
- Rovensky J,
- Srinivasaraghavan R,
- Bharadwaj SK,
- Spiegel R,
- Zatkova A,
Rheumatology, Osteoarthritis
1. Jan 2015
Association between biochemical cartilage markers and clinical symptoms in patients with hip osteoarthritis: cohort study with 2-year follow-up
OBJECTIVES:
To assess associations between uCTX-II or uCIIM and severity of hip pain in patients with mild-moderate hip osteoarthritis (OA) over a 2-year period, and establish whether the level of these biomarkers at baseline could estimate a specific trajectory of hip pain.
DESIGN:
A cohort st…
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Journal:
Authors:
- Dorleijn DM,
- Luijsterburg PA,
- Bay-Jensen AC,
- Siebuhr AS,
- Karsdal MA,
- Rozendaal RM,
- Bos PK,
- Bierma-Zeinstra SM,
Rheumatology, Gout
1. Jan 2015
Investigating the Robustness and Diagnostic Potential of Extracellular Matrix Remodelling Biomarkers in Alkaptonuria
BACKGROUND AND AIM:
Alkaptonuria (AKU) clinical manifestations resemble severe arthritis. The Suitability of Nitisinone in Alkaptonuria 1 (SONIA 1) study is a dose-finding trial for nitisinone treatment of AKU patients. We tested a panel of serum and urinary biomarkers reflecting extracellular matr…
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Journal:
Authors:
- Genovese F,
- Siebuhr AS,
- Musa K,
- Gallagher JA,
- Milan AM,
- Karsdal MA,
- Rovensky J,
- Bay-Jensen AC,
- Ranganath LR,
Rheumatology, Osteoarthritis
1. Jan 2015
Identifying specific profiles in patients with different degrees of painful knee osteoarthritis based on serological biochemical and mechanistic pain biomarkers: a diagnostic approach based on cluster analysis
Biochemical and pain biomarkers can be applied to patients with painful osteoarthritis profiles and may provide more details compared with conventional clinical tools. The aim of this study was to identify an optimal combination of biochemical and pain biomarkers for classification of patients with …
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Journal:
Authors:
- Egsgaard LL,
- Eskehave TN,
- Bay-Jensen AC,
- Hoeck HC,
- Arendt-Nielsen L,
Rheumatology, Spondyloarthropathies
18. Dec 2014
Biological relevance of citrullinations: diagnostic, prognostic and therapeutic options
OBJECTIVE:
Citrullination has become a hot topic within recent years due to its involvement in diseases such as rheumatoid arthritis (RA), multiple sclerosis and fibrosis. Citrullinations are the conversion of arginine to citrulline by peptidylarginine deiminase (PAD) enzymes, which affect protein …
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Journal:
Authors:
- Gudmann NS,
- Hansen NU,
- Jensen AC,
- Karsdal MA,
- Siebuhr AS,
Rheumatology, Osteoarthritis
11. Dec 2014
Association between experimental pain biomarkers and serologic markers in patients with different degrees of painful knee osteoarthritis
OBJECTIVE:
To assess the association between pain mechanisms (sensitization) and biochemical markers for cartilage, bone, and inflammation in patients with knee pain.
METHODS:
The study group comprised 281 patients with different degrees of knee pain intensity and radiographic findings (using t…
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Journal:
Authors:
- Arendt-Nielsen L,
- Eskehave TN,
- Egsgaard LL,
- Petersen KK,
- Graven-Nielsen T,
- Hoeck HC,
- Simonsen O,
- Siebuhr AS,
- Karsdal MA,
- Bay-Jensen AC,
Rheumatology, Osteoarthritis
4. Dec 2014
Suitability Of Nitisinone In Alkaptonuria 1 (SONIA 1): an international, multicentre, randomised, open-label, no-treatment controlled, parallel-group, dose-response study to investigate the effect of once daily nitisinone on 24-h urinary homogentisic acid excretion in patients with alkaptonuria after 4 weeks of treatment
BACKGROUND:
Alkaptonuria (AKU) is a serious genetic disease characterised by premature spondyloarthropathy. Homogentisate-lowering therapy is being investigated for AKU. Nitisinone decreases homogentisic acid (HGA) in AKU but the dose-response relationship has not been previously studied.
METHOD…
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Journal:
Authors:
- Ranganath LR,
- Milan AM,
- Hughes AT,
- Dutton JJ,
- Fitzgerald R,
- Briggs MC,
- Bygott H,
- Psarelli EE,
- Cox TF,
- Gallagher JA,
- Jarvis JC,
- van Kan C,
- Hall AK,
- Laan D,
- Olsson B,
- Szamosi J,
- Rudebeck M,
- Kullenberg T,
- Cronlund A,
- Svensson L,
- Junestrand C,
- Ayoob H,
- Timmis OG,
- Sireau N,
- Le Quan Sang KH,
- Genovese F,
- Braconi D,
- Santucci A,
- Nemethova M,
- Zatkova A,
- McCaffrey J,
- Christensen P,
- Ross G,
- Imrich R,
- Rovensky J,
Osteoarthritis, Rheumatology
17. Oct 2014
Cartilage turnover reflected by metabolic processing of type II collagen: a novel marker of anabolic function in chondrocytes
The aim of this study was to enable measurement of cartilage formation by a novel biomarker of type II collagen formation. The competitive enzyme-linked immunosorbent assay (ELISA) Pro-C2 was developed and characterized for assessment of the beta splice variant of type II procollagen (PIIBNP). This …
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Journal:
Authors:
- Gudmann NS,
- Wang J,
- Hoielt S,
- Chen P,
- Siebuhr AS,
- He Y,
- Christiansen TG,
- Karsdal MA,
- Bay-Jensen AC,
Extracellular Matrix Research, Rheumatology
22. Sep 2014
Type X collagen levels are elevated in serum from human osteoarthritis patients and associated with biomarkers of cartilage degradation and inflammation
BACKGROUND:
Osteoarthritis (OA) is the most common degenerative joint disease, of which the pathogenesis is inadequately understood. Hypertrophy-like changes have been observed as part of the progression of OA. The aim of the study was to develop and characterize a novel biomarker of chondrocytes h…
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Journal:
Authors:
- He Y,
- Siebuhr AS,
- Brandt-Hansen NU,
- Wang J,
- Su D,
- Zheng Q,
- Simonsen O,
- Petersen KK,
- Arendt-Nielsen L,
- Eskehave T,
- Hoeck HC,
- Karsdal MA,
- Bay-Jensen AC,
Rheumatology, Rheumatoid Arthritis
20. Sep 2014
Serological biomarkers of joint tissue turnover predict tocilizumab response at baseline
Rheumatoid arthritis (RA) is an autoimmune disease characterized by polyarticular joint inflammation resulting in massive tissue turnover. The turnover is partly mediated by an up-regulation of proteolytic enzymes, such as matrix metalloproteinases (MMPs).1 Matrix metalloproteinase 3 is 1 of the MMP…
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Journal:
Authors:
- Bay-Jensen AC,
- Byrjalsen I,
- Siebuhr AS,
- Christiansen C,
- Platt A,
- Karsdal MA,
Osteoarthritis
1. Sep 2014
Alpha C-telopeptide of type I collagen is associated with subchondral bone turnover and predicts progression of joint space narrowing and osteophytes in osteoarthritis
OBJECTIVE:
To evaluate joint tissue remodeling using the urinary collagen biomarkers urinary α-C-telopeptide of type I collagen (α-CTX) and urinary C-telopeptide of type II collagen (CTX-II) and to determine the association of these biomarkers with osteoarthritis (OA) severity, progression, and loc…
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Journal:
Authors:
- Huebner JL,
- Bay-Jensen AC,
- Huffman K,
- He Y,
- Leeming DJ,
- McDaniel GE,
- Karsdal MA,
- Kraus VB,
Rheumatology, Osteoarthritis
28. Aug 2014
Association Between Experimental Pain Biomarkers and Serological Markers in Patients With Different Degree of Painful Knee Osteoarthritis
OBJECTIVE:
To assess the association between pain mechanisms (sensitization) and biochemical markers for cartilage, bone, and inflammation in patients with knee pain.
METHODS:
The study group comprised 281 patients with different degrees of knee pain intensity and radiographic findings (using t…
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Journal:
Authors:
- Arendt-Nielsen L,
- Eskehave TN,
- Egsgaard LL,
- Petersen KK,
- Graven-Nielsen T,
- Hoeck HC,
- Simonsen O,
- Siebuhr AS,
- Karsdal MA,
- Bay-Jensen AC,
Rheumatology, Osteoarthritis
1. Aug 2014
Biomarkers of cartilage and surrounding joint tissue
The identification and clinical demonstration of efficacy and safety of osteo- and chondro-protective drugs are met with certain difficulties. During the last few decades, the pharmaceutical industry has, in the field of rheumatology, experienced disappointments associated with the development of di…
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Journal:
Authors:
- Siebuhr AS,
- He Y,
- Gudmann NS,
- Gram A,
- Kjelgaard-Petersen CF,
- Qvist P,
- Karsdal MA,
- Bay-Jensen AC,
Rheumatology, Osteoarthritis
23. Jul 2014
Meta-analysis identifies loci affecting levels of the potential osteoarthritis biomarkers sCOMP and uCTX-II with genome wide significance
BACKGROUND:
Research for the use of biomarkers in osteoarthritis (OA) is promising, however, adequate discrimination between patients and controls may be hampered due to innate differences. We set out to identify loci influencing levels of serum cartilage oligomeric protein (sCOMP) and urinary C-te…
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Journal:
Authors:
- Ramos YF,
- Metrustry S,
- Arden NK,
- Bay-Jensen AC,
- Beekman M,
- de Craen AJ,
- Cupples LA,
- Esko T,
- Evangelou E,
- Felson DT,
- Hart DJ,
- Ioannidis JP,
- Karsdal MA,
- Kloppenburg M,
- Lafeber F,
- Metspalu A,
- Panoutsopoulou K,
- Slagboom PE,
- Spector TD,
- van Spil EW,
- Uitterlinden AG,
- Zhu Y,
- Valdes AM,
- van Meurs JB,
- Meulenbelt I,
Bone, Rheumatology, Osteoarthritis
6. Jun 2014
ALPHA-CTX is associated with subchondral bone turnover and predicts progression of joint space narrowing and osteophytes in osteoarthritis
OBJECTIVE:
To evaluate joint tissue remodeling, with urinary collagen biomarkers, uALPHA CTX and uCTXII, and their association with osteoarthritis (OA) severity, progression, and localized knee bone turnover.
METHODS:
Participants (N=149) with symptomatic and radiographic knee OA underwent fixe…
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Journal:
Authors:
- Huebner JL,
- Bay-Jensen AC,
- Huffman KM,
- He Y,
- Leeming DJ,
- McDaniel GE,
- Karsdal MA,
- Kraus VB,
Osteoarthritis
22. May 2014
Large scale meta-analysis of urinary C-terminal telopeptide, serum cartilage oligomeric protein and matrix metalloprotease degraded type II collagen and their role in prevalence, incidence and progression of osteoarthritis
OBJECTIVE:
To evaluate the role of three cartilage-derived biomarkers on osteoarthritis (OA): urinary C-terminal telopeptide (uCTX-II), serum cartilage oligomeric protein (sCOMP), and serum MMP degraded type II collagen (sC2M).
SUBJECTS AND METHODS:
Samples from 3582 individuals from the Rotter…
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Journal:
Authors:
- Valdes AM,
- Meulenbelt I,
- Chassaing E,
- Arden NK,
- Bierma-Zeinstra S,
- Hart D,
- Hofman A,
- Karsdal MA,
- Kloppenburg M,
- Kroon HM,
- Slagboom EP,
- Spector TD,
- Uitterlinden AG,
- van Meurs JB,
- Bay-Jensen AC,
Osteoarthritis
19. Mar 2014
The active form of MMP-3 is a marker of synovial inflammation and cartilage turnover in inflammatory joint diseases
BACKGROUND:
Matrix metalloproteinase-3 (MMP-3) plays an important role in the pathology of rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Measurement of active MMP-3 in clinical samples could provide information about progression of rheumatoid diseases, and potentially response to treat…
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Journal:
Authors:
- Sun S,
- Bay-Jensen AC,
- Karsdal MA,
- Siebuhr AS,
- Zheng Q,
- Maksymowych WP,
- Christiansen TG,
- Henriksen K,
Rheumatology, Osteoarthritis
1. Mar 2014
Republished: Value of biomarkers in osteoarthritis: current status and perspectives
Osteoarthritis affects the whole joint structure with progressive changes in cartilage, menisci, ligaments and subchondral bone, and synovial inflammation. Biomarkers are being developed to quantify joint remodelling and disease progression. This article was prepared following a working meeting of t…
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Journal:
Authors:
- Lotz M,
- Martel-Pelletier J,
- Christiansen C,
- Brandi ML,
- Bruyère O,
- Chapurlat R,
- Collette J,
- Cooper C,
- Giacovelli G,
- Kanis JA,
- Karsdal MA,
- Kraus V,
- Lems WF,
- Meulenbelt I,
- Pelletier JP,
- Raynauld JP,
- Reiter-Niesert S,
- Rizzoli R,
- Sandell LJ,
- Van Spil WE,
- Reginster JY,
Rheumatology, Osteoarthritis
6. Feb 2014
The coupling of bone and cartilage turnover in osteoarthritis: opportunities for bone antiresorptives and anabolics as potential treatments?
Osteoarthritis (OA) is the most common form of arthritic disease, and a major cause of disability and impaired quality of life in the elderly. OA is a complex disease of the entire joint, affecting bone, cartilage and synovium that thereby presents multiple targets for treatment. This manuscript wil…
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Journal:
Authors:
- Karsdal MA,
- Bay-Jensen AC,
- Lories RJ,
- Abramson S,
- Spector T,
- Pastoureau P,
- Christiansen C,
- Attur M,
- Henriksen K,
- Goldring SR,
- Kraus V,
Rheumatology, Rheumatoid Arthritis
5. Feb 2014
Effect of tocilizumab combined with methotrexate on circulating biomarkers of synovium, cartilage, and bone in the LITHE study
OBJECTIVE:
We investigated the effects of tocilizumab (TCZ) on joint tissue remodeling in patients with moderate to severely active RA by measuring tissue-specific biomarker.
METHODS:
The LITHE biomarker study (n = 740) was a phase III study of 4- and 8-mg/kg TCZ in combination with MTX. Early …
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Journal:
Authors:
- Bay-Jensen AC,
- Platt A,
- Byrjalsen I,
- Vergnoud P,
- Christiansen C,
- Karsdal MA,
Rheumatology, Rheumatoid Arthritis
27. Jan 2014
Rheumatoid arthritis - A case for Personalized Health Care?
Ethical, clinical, and economic considerations highlight the pressing need to advance the identification of optimal treatments for each individual patient. Personalized health care (PHC) may provide a significant benefit in the treatment of a number of clinical indications characterized by costly th…
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Journal:
Authors:
- Karsdal MA,
- Bay-Jensen AC,
- Henriksen K,
- Christiansen C,
- Genant HK,
- Chamberlain C,
- Platt A,
Rheumatology, Osteoarthritis
22. Jan 2014
Osteoarthritis--a case for personalized health care?
For both economic and ethical reasons, identification of the optimal treatment for each individual patient is a pressing concern, not only for the patients and their physician, but also health care payers and the pharmaceutical industry. In the field of osteoarthritis (OA) this is of particular rele…
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Journal:
Authors:
- Karsdal MA,
- Christiansen C,
- Ladel C,
- Henriksen K,
- Kraus VB,
- Bay-Jensen AC,
Rheumatology, Osteoarthritis
7. Jan 2014
Identification and characterisation of osteoarthritis patients with inflammation derived tissue turnover
OBJECTIVES:
Osteoarthritis (OA) is a degenerative disease with a subset of patients experiencing joint inflammation, but C-reactive protein (CRP) has shown limited use in OA as a diagnostic marker. The aim was to identify subpopulations of patients with high or low levels of acute (high sensitive C…
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Journal:
Authors:
- Siebuhr AS,
- Petersen KK,
- Arendt-Nielsen L,
- Egsgaard LL,
- Eskehave T,
- Christiansen C,
- Simonsen O,
- Hoeck HC,
- Karsdal MA,
- Bay-Jensen AC,
Rheumatology
12. Dec 2013
Type VI collagen turnover-related peptides-novel serological biomarkers of muscle mass and anabolic response to loading in young men
BACKROUND:
Immobilization-induced loss of muscle mass is a complex phenomenon with several parallels to sarcopenic and cachectic muscle loss. Muscle is a large organ with a protein turnover that is orders of magnitude larger than most other tissues. Thus, we hypothesize that muscle loss and regain …
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Journal:
Authors:
- Nedergaard A,
- Sun S,
- Karsdal MA,
- Henriksen K,
- Kjær M,
- Lou Y,
- He Y,
- Zheng Q,,
- Suetta C,
Rheumatology, Osteoarthritis
12. Nov 2013
Value of biomarkers in osteoarthritis: current status and perspectives
Osteoarthritis affects the whole joint structure with progressive changes in cartilage, menisci, ligaments and subchondral bone, and synovial inflammation. Biomarkers are being developed to quantify joint remodelling and disease progression. This article was prepared following a working meeting of t…
Read the publication
Journal:
Authors:
- Lotz M,
- Martel-Pelletier J,
- Christiansen C,
- Brandi ML,
- Bruyère O,
- Chapurlat R,
- Collette J,
- Cooper C,
- Giacovelli G,
- Kanis JA,
- Karsdal MA,
- Kraus V,
- Lems WF,
- Meulenbelt I,
- Pelletier JP,
- Raynauld JP,
- Reiter-Niesert S,
- Rizzoli R,
- Sandell LJ,
- Van Spil WE,
- Reginster JY,
Rheumatology, Osteoarthritis
17. Oct 2013
Metabolic health in families enriched for longevity is associated with low prevalence of hand osteoarthritis and influences OA biomarker profiles
OBJECTIVES:
Individual metabolic characteristics and age-related changes may affect osteoarthritis (OA) risk as well as levels of potential OA biomarkers such as serum cartilage oligomeric protein (sCOMP) and urinary cross-linked C-telopeptide of type 2 collagen (uCTX2). We investigated hand OA and…
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Journal:
Authors:
- Bos SD,
- Beekman M,
- Maier AB,,
- Karsdal MA,
- Kwok WY,
- Bay-Jensen AC,
- Kloppenburg M,
- Slagboom PE,
- Meulenbelt I,
Rheumatology
16. Oct 2013
Musculoskeletal ageing and primary prevention
Loss of musculoskeletal mass and function is a natural ageing trait, reinforced by an unhealthy life style. Loss of bone (osteoporosis) and muscle (sarcopaenia) are conditions whose prevalence are increasing because of the change in population distribution in the western world towards an older mean …
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Journal:
Authors:
- Nedergaard A,
- Henriksen K,
- Karsdal MA,
- Christiansen C,
Rheumatology, Osteoarthritis
6. Oct 2013
The development and characterization of an ELISA specifically detecting the active form of cathepsin K
OBJECTIVE:
Cathepsin K plays essential roles in bone resorption and is intensely investigated as a therapeutic target for the treatment of osteoporosis. Hence an assessment of the active form of cathepsin K may provide important biological information in metabolic bone diseases, such as osteoporosi…
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Journal:
Authors:
- Sun S,
- Karsdal MA,
- Bay-Jensen AC,
- Sørensen MG,
- Zheng Q,
- Dziegiel MH,
- Maksymowych WP,
- Henriksen K,
Rheumatology, Osteoarthritis
14. Aug 2013
Serological identification of fast progressors of structural damage with rheumatoid arthritis
INTRODUCTION:
Rheumatoid arthritis (RA) patients with structural progression are in most need of immediate treatment to maintain tissue integrity. The serum protein fingerprint, type I collagen degradation mediated by matrix metalloproteinases (MMP)-cleavage (C1M), is a biomarker of tissue destruct…
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Journal:
Authors:
- Siebuhr AS,
- Bay-Jensen AC,
- Leeming DJ,
- Plat A,
- Byrjalsen I,
- Christiansen C,
- van de Heijde D,
- Karsdal MA,
Rheumatology, Spondyloarthropathies
1. Aug 2013
Circulating protein fragments of cartilage and connective tissue degradation are diagnostic and prognostic markers of rheumatoid arthritis and ankylosing spondylitis
Inflammation driven connective tissue turnover is key in rheumatic diseases, such as ankylosing spondylitis (AS). Few biomarkers are available for measuring disease prognosis or the efficacy of interventions applied in these tissue-related conditions. Type II collagen is the primary structural prote…
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Journal:
Authors:
- Bay-Jensen AC,
- Wichuk S,
- Byrjalsen I,
- Leeming DJ,
- Morency N,
- Christiansen C,
- Karsdal MA,
- Maksymowych WP,
Rheumatology, Rheumatoid Arthritis
31. May 2013
Quantification of "end products" of tissue destruction in inflammation may reflect convergence of cytokine and signaling pathways - implications for modern clinical chemistry
The degree of inflammation in auto-immune diseases such as rheumatoid arthritis is often assessed in serum and used for diagnostic and prognostic purposes. The serum levels of acute inflammatory signaling molecules (C-reactive protein and serum amyloid A) in conjunction with the important pro-inflam…
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Journal:
Authors:
Rheumatology, Osteoarthritis
13. May 2013
Role of hormones in cartilage and joint metabolism: understanding an unhealthy metabolic phenotype in osteoarthritis
OBJECTIVE:
Joint health is affected by local and systemic hormones. It is well accepted that systemic factors regulate the metabolism of joint tissues, and that substantial cross-talk between tissues actively contributes to homeostasis. In the current review, we try to define a subtype of osteoarth…
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Journal:
Authors:
- Bay-Jensen AC,
- Slagboom E,
- Chen-An P,
- Alexandersen P,
- Qvist P,
- Christiansen C,
- Meulenbelt I,
- Karsdal MA,
Rheumatology, Osteoarthritis
24. Apr 2013
The development and characterization of a competitive ELISA for measuring active ADAMTS-4 in a bovine cartilage ex vivo model
ADAMTS-4 (aggrecanase1) is believed to play an important role in the degradation of aggrecan during the progression of joint diseases. ADAMTS-4 is synthesized as a latent pro-enzyme that requires the removal of the pro-domain, exposing the N-terminal neoepitope, to achieve activity. We developed a m…
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Journal:
Authors:
- He Y,
- Zheng Q,
- Simonsen O,
- Petersen KK,
- Christiansen TG,
- Karsdal MA,
- Bay-Jensen AC,
Rheumatology, Spondyloarthropathies
4. Apr 2013
Circulating citrullinated vimentin fragments reflect disease burden in ankylosing spondylitis and have prognostic capacity for radiographic progression
OBJECTIVE:
Ankylosing spondylitis (AS) has been considered a seronegative rheumatic disease based on absent or low levels of antibodies against citrullinated proteins. The present study was undertaken to evaluate whether a citrullinated and matrix metalloproteinase-degraded fragment of vimentin (VI…
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Journal:
Authors:
- Bay-Jensen AC,
- Karsdal MA,
- Vassiliadis E,
- Marcher-Mikkelsen K,
- Lories R,
- Christiansen C,
- Maksymowych WP,
Rheumatology, Osteoarthritis
14. Feb 2013
Investigation of chondrocyte hypertrophy and cartilage calcification in a full-depth articular cartilage explants model
Articular cartilage deterioration, which includes cartilage degradation and chondrocyte hypertrophy, is a hallmark of degenerative joint diseases (DJD). Chondrocyte hypertrophy is initiated in the deep layer of the cartilage; thus, a robust explants model for investigation of hypertrophy should incl…
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Journal:
Authors:
- Chen-An P,
- Andreassen KV,
- Henriksen K,
- Karsdal MA,
- Bay-Jensen AC,
Rheumatology, Osteoarthritis
3. Jan 2013
Bringing cancer serological diagnosis to a new level: focusing on HER2, protein ectodomain shedding and neoepitope technology
Cancer is a heterogeneous disease and consequently an exact diagnosis is as important as the actual therapy. Therefore, identification of novel diagnostic biomarker targets is urgently needed. Physiological and pathological changes are reflected by post-translational modifications of proteins. Each …
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Journal:
Authors:
- Wang J,
- Willumsen N,
- Zheng Q,
- Xue Y,
- Karsdal M,
- Bay-Jensen AC,
Rheumatology, Osteoarthritis
18. Dec 2012
The pathogenesis of osteoarthritis involves bone, cartilage and synovial inflammation: may estrogen be a magic bullet?
The female predominance of polyarticular osteoarthritis (OA), and in particular the marked increase of OA in women after the menopause points to a likely involvement of female sex hormones in the maintenance of cartilage homeostasis. This perception has inspired many research groups to investigate t…
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Journal:
Authors:
Rheumatology, Spondyloarthropathies
17. Nov 2012
Ankylosing spondylitis is characterized by an increased turnover of several different metalloproteinase-derived collagen species: a cross-sectional study
Ankylosing spondylitis (AS) is characterized by gradual cementation of the vertebrae, a process that is described by excessive extracellular matrix remodeling. Specific matrix metalloproteinase (MMP)-derived collagen fragments are released to the circulation, and measurement of those might act as bi…
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Journal:
Authors:
- Bay-Jensen AC,
- Leeming DJ,
- Kleyer A,
- Veidal SS,
- Schett G,
- Karsdal MA,
Rheumatology, Rheumatoid Arthritis
4. Oct 2012
IL-6 receptor inhibition positively modulates bone balance in rheumatoid arthritis patients with an inadequate response to anti-tumor necrosis factor therapy: biochemical marker analysis of bone metabolism in the tocilizumab RADIATE study (NCT00106522)
OBJECTIVE:
To evaluate changes in biochemical markers of bone metabolism in response to tocilizumab in patients with anti-tumor necrosis factor-refractory rheumatoid arthritis (RA).
METHODS:
RADIATE was a randomized, double-blind, placebo-controlled, parallel-group phase 3 trial. C-reactive pro…
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Journal:
Authors:
- Karsdal MA,
- Schett G,
- Emery P,
- Harari O,
- Byrjalsen I,
- Kenwright A,
- Bay-Jensen AC,
- Platt A,
Rheumatology, Rheumatoid Arthritis
20. Sep 2012
Matrix metalloproteinase-dependent turnover of cartilage, synovial membrane, and connective tissue is elevated in rats with collagen induced arthritis
BACKGROUND:
Rheumatoid arthritis is a disease affecting the extracellular matrix of especially synovial joints. The thickness of the synovial membrane increases and surrounding tissue degrades, leading to altered collagen balance in the tissues. In this study, we investigated the altered tissue bal…
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Journal:
Authors:
- Siebuhr AS,
- Wang J,
- Karsdal MA,
- Bay-Jensen AC,
- Y J,
- Q Z,
Rheumatology, Osteoarthritis
1. Jul 2012
The inhibitory effect of salmon calcitonin on tri-iodothyronine induction of early hypertrophy in articular cartilage
OBJECTIVE:
Salmon calcitonin has chondroprotective effect both in vitro and in vivo, and is therefore being tested as a candidate drug for cartilage degenerative diseases. Recent studies have indicated that different chondrocyte phenotypes may express the calcitonin receptor (CTR) differentially. W…
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Journal:
Authors:
- Chen-An P,
- Andreassen KV,
- Henriksen K,
- Karsdal MA,
- Bay-Jensen AC,
Rheumatology, Spondyloarthropathies
30. May 2012
Investigation of two novel biochemical markers of inflammation, matrix metalloproteinase and cathepsin generated fragments of C-reactive protein, in patients with ankylosing spondylitis
OBJECTIVES:
Ankylosing spondylitis (AS) is a chronic inflammation of the spine and the sacroiliac joints. Current markers of inflammation, such as C-reactive protein (CRP), are reflecting the production of an acute phase reactant rather than tissue specific inflammation, but the use of CRP as a dia…
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Journal:
Authors:
- Skjøt-Arkil H,
- Schett G,
- Zhang C,
- Larsen DV,
- Wang Y,
- Zheng Q,
- Larsen MR,
- Nawrocki A,
- Bay-Jensen AC,
- Henriksen K,
- Christiansen C,
- Alexandersen P,
- Leeming DJ,
- Karsdal MA,
Rheumatology, Spondyloarthropathies
7. May 2012
MMP mediated type V collagen degradation (C5M) is elevated in ankylosing spondylitis
OBJECTIVES:
Type V collagen has been demonstrated to control fibril formation. The aim of this study was to develop an ELISA capable of detecting a fragment of type V collagen generated by MMP-2/9 and to evaluate the assay as biomarker for ankylosing spondylitis (AS).
DESIGN AND METHODS:
A frag…
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Journal:
Authors:
- Veidal SS,
- Larsen DV,
- Chen X,
- Sun S,
- Zheng Q,
- Bay-Jensen AC,
- Leeming DJ,
- Nawrocki A,
- Larsen MR,
- Schett G,
- Karsdal MA,
Rheumatology, Osteoarthritis
15. Feb 2012
Mice over-expressing salmon calcitonin have strongly attenuated osteoarthritic histopathological changes after destabilization of the medial meniscus
OBJECTIVE:
Calcitonin is well-known for its inhibitory actions on bone-resorbing osteoclasts and recently potential beneficial effects on cartilage were shown. We investigated effects of salmon calcitonin (sCT) on the articular cartilage and bone, after destabilization of the medial meniscus (DMM) …
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Journal:
Authors:
- Sondergaard BC,
- Catala-Lehnen P,
- Huebner AK,
- Bay-Jensen AC,
- Schinke T,
- Henriksen K,
- Schilling S,
- Haberland M,
- Nielsen RH,
- Amling M,
- Karsdal MA,
Rheumatology, Osteoarthritis
18. Jan 2012
The distribution pattern of critically short telomeres in human osteoarthritic knees
INTRODUCTION
Telomere shortening is associated with a number of common age-related diseases. A role of telomere shortening in osteoarthritis (OA) has been suggested, mainly based on the assessment of mean telomere length in ex vivo expanded chondrocytes. We addressed this role directly in vivo by u…
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Journal:
Authors:
- Harbo M,
- Bendix L,
- Bay-Jensen AC,
- Graakjaer J,
- Søe K,
- Andersen TL,
- Kjaersgaard-Andersen P,
- Koelvraa S,
- Delaisse JM,
Rheumatology, Osteoarthritis, Rheumatoid Arthritis
8. Dec 2011
Molecular serum and urine marker repertoire supporting clinical research on joint diseases
The need for improved analytical techniques in the study of slow, degenerative diseases such as rheumatoid arthritis and osteoarthritis has driven major efforts aimed at identifying biochemical markers of pathological processes in both diseases. A series of novel biochemical markers has surfaced and…
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Journal:
Authors:
- Qvist P,
- Bay-Jensen AC,
- Christiansen C,
- Sondergaard BC,
- Karsdal MA,
Rheumatology, Osteoarthritis
13. Oct 2011
Identification of the calcitonin receptor in osteoarthritic chondrocytes
BACKGROUND:
Preclinical and clinical studies have shown that salmon calcitonin has cartilage protective effects in joint degenerative diseases, such as osteoarthritis (OA). However, the presence of the calcitonin receptor (CTR) in articular cartilage chondrocytes is yet to be identified. In this st…
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Journal:
Authors:
- Segovia-Silvestre T,
- Bonnefond C,
- Sondergaard BC,
- Christensen T,
- Karsdal MA,
- Bay-Jensen AC,
Rheumatology, Osteoarthritis
14. Jul 2011
Characterization of an Ex vivo Femoral Head Model Assessed by Markers of Bone and Cartilage Turnover
OBJECTIVE:
The pathophysiology of osteoarthritis involves the whole joint and is characterized by cartilage degradation and altered subchondral bone turnover. At present, there is a need for biological models that allow investigation of the interactions between the key cellular players in bone/cart…
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Journal:
Authors:
- Madsen SH,
- Goettrup AS,
- Thomsen G,
- Christensen ST,
- Schultz N,
- Henriksen K,
- Bay-Jensen AC,
- Karsdal MA,
Rheumatology, Osteoarthritis
19. Apr 2011
Oral salmon calcitonin reduces cartilage and bone pathology in an osteoarthritis rat model with increased subchondral bone turnover
OBJECTIVES:
Traumatic osteoarthritis (OA) is possibly augmented by effects from loss of sex hormones. Salmon calcitonin is shown to reduce OA pathogenesis and bone resorption. We investigated the effects of oral salmon calcitonin treatment and ovariectomy on cartilage and bone pathology in a trauma…
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Journal:
Authors:
- Nielsen RH,
- Bay-Jensen AC,
- Byrjalsen I,
- Karsdal MA,
Rheumatology, Osteoarthritis
13. Apr 2011
Enzyme-linked immunosorbent assay (ELISAs) for metalloproteinase derived type II collagen neoepitope, CIIM--increased serum CIIM in subjects with severe radiographic osteoarthritis
OBJECTIVES:
In joint degenerative diseases, the collagens are degraded by matrix metalloproteinases and protein fragments are released to serum as potential biomarkers.
METHODS:
A collagen type II specific neoepitope, CIIM, was identified (…RDGAAG(1053)) by mass spectrometry. Two ELISAs against…
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Journal:
Authors:
- Bay-Jensen AC,
- Liu Q,
- Byrjalsen I,
- Li Y,
- Wang J,
- Pedersen C,
- Leeming DJ,
- Dam EB,
- Zheng Q,
- Qvist P,
- Karsdal MA,
Rheumatology, Spondyloarthropathies
8. Apr 2011
Biochemical markers of ongoing joint damage in rheumatoid arthritis--current and future applications, limitations and opportunities
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease associated with potentially debilitating joint inflammation, as well as altered skeletal bone metabolism and co-morbid conditions. Early diagnosis and aggressive treatment to control disease activity offers the highest likelihood of …
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Journal:
Authors:
- Karsdal MA,
- Woodworth T,
- Henriksen K,
- Maksymowych WP,
- Genant H,
- Vergnaud P,
- Christiansen C,
- Schubert T,
- Qvist P,
- Schett G,
- Platt A,
- Bay-Jensen AC,
Rheumatology, Systemic Sclerosis
29. Mar 2011
Measurement of matrix metalloproteinase 9-mediated collagen type III degradation fragment as a marker of skin fibrosis
BACKGROUND:
The current study utilized a Bleomycin-induced model of skin fibrosis to investigate the neo-epitope CO3-610 (KNGETGPQGP), a fragment of collagen III released during matrix metalloproteinase-9 (MMP9) degradation of the protein, we have previously described as a novel biomarker for liver…
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Journal:
Authors:
- Vassiliadis E,
- Veidal SS,
- Barascuk N,
- Mullick JB,
- Clausen RE,
- Larsen L,
- Simonsen H,
- Larsen DV,
- bay,
- Segovia-Silvestre T,
- Leeming DJ,
- Karsdal MA,
Rheumatology, Osteoarthritis
15. Mar 2011
A microarray analysis of full depth knee cartilage of ovariectomized rats
BACKGROUND:
This short communication focuses the on articular cartilage and the subchondral bone, both of which play important roles in the development of osteoarthritis (OA). There are indications that estrogen-deficiency, as the post-menopausal state, accelerate the development of OA.
FINDINGS…
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Journal:
Authors:
- Bay-Jensen AC,
- Nielsen RH,
- Segovia-Silvestre T,
- Azria M,
- Staedtler F,
- Letzkus M,
- Hartmann N,
- Brachat AH,
- Karsdal MA,
Rheumatology, Osteoarthritis
3. Jan 2011
Tummala SDiagnosis of Osteoarthritis by Cartilage Surface Smoothness Quantified Automatically from Knee MRI
OBJECTIVE:
We investigated whether surface smoothness of articular cartilage in the medial tibiofemoral compartment quantified from magnetic resonance imaging (MRI) could be appropriate as a diagnostic marker of osteoarthritis (OA).
METHOD:
At baseline, 159 community-based subjects aged 21 to 8…
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Journal:
Authors:
- Tummala S,
- Bay-Jensen AC,
- Karsdal MA,
- Dam EB,
Rheumatology, Osteoarthritis
17. Jun 2010
Biochemical markers identify influences on bone and cartilage degradation in osteoarthritis--the effect of sex, Kellgren-Lawrence (KL) score, body mass index (BMI), oral salmon calcitonin (sCT) treatment and diurnal variation
BACKGROUND:
Osteoarthritis (OA) involves changes in both bone and cartilage. These processes might be associated under some circumstances. This study investigated correlations between bone and cartilage degradation in patients with OA as a function of sex, Kellgren-Lawrence (KL) score, Body Mass In…
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Journal:
Authors:
Rheumatology, Osteoarthritis
15. May 2010
Aggrecanase- and matrix metalloproteinase-mediated aggrecan degradation is associated with different molecular characteristics of aggrecan and separated in time ex vivo
Aggrecan is one of the first proteins to be depleted from articular cartilage in early osteoarthritis. We investigated the molecular differences between matrix metalloproteinase (MMP)- and aggrecanase-mediated aggrecan degradation, as a consequence of their distinct time-dependent degradation profil…
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Journal:
Authors:
- Madsen SH,
- Sumer EU,
- Bay-Jensen AC,
- Sondergaard BC,
- Qvist P,
- Karsdal MA,
Rheumatology, Osteoarthritis
5. Apr 2010
Investigation of the direct effects of salmon calcitonin on human osteoarthritic chondrocytes
BACKGROUND:
Calcitonin has been demonstrated to have chondroprotective effects under pre-clinical settings. It is debated whether this effect is mediated through subchondral-bone, directly on cartilage or both in combination. We investigated possible direct effects of salmon calcitonin on proteogly…
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Journal:
Authors:
- Sondergaard BC,
- Madsen SH,
- Segovia-Silvestre T,
- Paulsen SJ,
- Christiansen T,
- Pedersen C,
- Bay-Jensen AC,
- Karsdal MA,
Rheumatology, Osteoarthritis
28. Feb 2010
Which elements are involved in reversible and irreversible cartilage degradation in osteoarthritis?
Osteoarthritis (OA) is a disease of the entire joint. Different treatment strategies for OA have been proposed and tested clinically without the desired efficacy. One reason for the scarcity of current chondroprotective agents may be the insufficient understanding of the patho-physiology of the join…
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Journal:
Authors:
- Bay-Jensen AC,
- Hoegh-Madsen S,
- Dam E,
- Henriksen K,
- Sondergaard BC,
- Pastoureau P,
- Qvist P,
- Karsdal MA,
Rheumatology, Osteoarthritis
15. Feb 2010
Application of biochemical markers in development of drugs for treatment of osteoarthritis
Osteoarthritis is a chronic disease for which no efficacious medical intervention is yet available. Recent disappointments in late-stage clinical development of disease-modifying osteoarthritic drugs (DMOADs) have precipitated efforts in biomarker discovery aimed at developing an analytical tool box…
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Journal:
Authors:
- Qvist P,
- Christiansen C,
- Karsdal MA,
- Madsen SH,
- Sondergaard BC,
- Bay-Jensen AC,
Rheumatology
8. Feb 2010
Biochemical markers of joint tissue turnover
Recent disappointments in late stage developments of anti-osteoarthritic drugs have reinforced efforts to develop better biomarkers for application in both the drug development process as well as in the routine management of these patients. Here we provide a brief review of biochemical tests availab…
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Journal:
Authors:
- Bay-Jensen AC,
- Sondergaard BC,
- Christiansen C,
- Karsdal MA,
- Madsen SH,
- Qvist P,
Rheumatology, Osteoarthritis
2. Feb 2010
Biglycan and fibromodulin have essential roles in regulating chondrogenesis and extracellular matrix turnover in temporomandibular joint osteoarthritis
The temporomandibular joint is critical for jaw movements and allows for mastication, digestion of food, and speech. Temporomandibular joint osteoarthritis is a degenerative disease that is marked by permanent cartilage destruction and loss of extracellular matrix (ECM). To understand how the ECM re…
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Journal:
Authors:
- Embree MC,
- Kilts TM,
- Ono M,
- Inkson CA,
- Syed-Picard F,
- Karsdal MA,
- Oldberg A,
- Bi Y,
- Young MF,
Rheumatology, Osteoarthritis
18. Dec 2009
Suppression of MMP activity in bovine cartilage explants cultures has little if any effect on the release of aggrecanase-derived aggrecan fragments
Progressive loss of articular cartilage is a central hallmark in many joint disease, however, the relative importance of individual proteolytic pathways leading to cartilage erosion is at present unknown. We therefore investigated the time-dependant release ex vivo of MMP- and aggrecanase-derived fr…
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Journal:
Authors:
- Wang B,
- Chen P,
- Jensen AC,
- Karsdal MA,
- Madsen SH,
- Sondergaard BC,
- Zheng Q,
- Qvist P,
Rheumatology, Osteoarthritis
24. Jul 2009
Identification of progressors in osteoarthritis by combining biochemical and MRI-based markers
INTRODUCTION:
At present, no disease-modifying osteoarthritis drugs (DMOADS) are approved by the FDA (US Food and Drug Administration); possibly partly due to inadequate trial design since efficacy demonstration requires disease progression in the placebo group. We investigated whether combinations…
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Journal:
Authors:
- Dam EB,
- Loog M,
- Christiansen C,
- Byrjalsen I,
- Folkesson J,
- Nielsen M,
- Qazi AA,
- Pettersen PC,
- Garnero P,
- Karsdal MA,
Rheumatology, Osteoarthritis
15. Jun 2009
Cartilage formation measured by a novel PIINP assay suggests that IGF-I does not stimulate but maintains cartilage formation ex vivo
OBJECTIVES:
The aim of this study was to investigate the time-dependent effect of insulin-like growth factor-I (IGF)-I on cartilage, evaluated by a novel procollagen type II N-terminal propeptide (PIINP) formation assay. This was performed in a cartilage model.
METHODS:
Bovine articular cartila…
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Journal:
Authors:
- Madsen SH,
- Sondergaard BC,
- Bay-Jensen AC,
- Karsdal MA,
Rheumatology, Osteoarthritis
31. Aug 2008
Characterization of metalloprotease cleavage products of human articular cartilage
OBJECTIVE:
To identify, characterize, and compare proteolysis peptide products generated by metalloprotease digests of human articular cartilage.
METHODS:
Human articular cartilage was digested by the addition of exogenous metalloproteases, including matrix metalloproteinases 2, 3, 8, 9, 12, an…
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Journal:
Authors:
- Zhen EY,
- Brittain IJ,
- Laska DA,
- Mitchell PG,
- Sumer EU,
- Karsdal MA,
- Duffin KL,
Rheumatology, Osteoarthritis
16. Jun 2008
Should subchondral bone turnover be targeted when treating osteoarthritis?
OBJECTIVE:
Osteoarthritis (OA) is the most common form of arthritic disease, and it is a major cause of disability and impaired quality of life in the elderly. OA is a complex disease of the entire joint, including bone and cartilage, thereby presenting alternative approaches for treatment. This re…
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Journal:
Authors:
- Karsdal MA,
- Leeming DJ,
- Dam EB,
- Henriksen K,
- Alexandersen P,
- Pastoureau P,
- Altman RD,
- Christiansen C,
Rheumatology, Osteoarthritis
6. Jun 2008
Automatic quantification of local and global articular cartilage surface curvature: biomarkers for osteoarthritis
The objective of this study was to quantitatively assess the surface curvature of the articular cartilage from low-field magnetic resonance imaging (MRI) data, and to investigate its role in populations with varying radiographic signs of osteoarthritis (OA), cross-sectionally and longitudinally. The…
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Journal:
Authors:
- Folkesson J,
- Dam EB,
- Olsen OF,
- Karsdal MA,
- Pettersen PC,
- Christiansen C,
Rheumatology, Osteoarthritis
8. May 2008
Cartilage degradation is fully reversible in the presence of aggrecanase but not matrix metalloproteinase activity
INTRODUCTION:
Physiological and pathophysiological cartilage turnover may coexist in articular cartilage. The distinct enzymatic processes leading to irreversible cartilage damage, compared with those needed for continuous self-repair and regeneration, remain to be identified. We investigated the c…
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Journal:
Authors:
- Karsdal MA,
- Madsen SH,
- Christiansen C,
- Henriksen K,
- Fosang AJ,
- Sondergaard BC,
Rheumatology, Osteoarthritis
10. Apr 2008
Oestrogen exhibits type II collagen protective effects and attenuates collagen-induced arthritis in rats
As anti-inflammatory treatments used in rheumatoid arthritis, such as glucocorticoids, often result in secondary detrimental effects on bone health, the objective of this study was to investigate the effects of oestrogen therapy (ET) on the development and activity of collagen-induced arthritis (CIA…
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Journal:
Authors:
- Nielsen RH,
- Christiansen C,
- Stolina M,
- Karsdal MA,
Rheumatology, Osteoarthritis
13. Feb 2008
Evaluation of cartilage damage by measuring collagen degradation products in joint extracts in a traumatic model of osteoarthritis
The objective of this work was to investigate whether collagen degradation products in protein extract from joints could provide quantitative information on cartilage damage. Osteoarthritis (OA) was surgically induced in rat knee joints. Joints were isolated 7, 14 and 28 days after surgery for prote…
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Journal:
Authors:
- Nielsen RH,
- Stoop R,
- Leeming DJ,
- Stolina M,
- Qvist P,
- Christiansen C,
- Karsdal MA,
Rheumatology, Osteoarthritis
11. Feb 2008
An update review of cellular mechanisms conferring the indirect and direct effects of estrogen on articular cartilage
OBJECTIVE:
To review cellular mechanisms that have been proposed to mediate the indirect and direct effects of estrogen on articular cartilage, and to outline the remaining clinical questions that need to be clarified before utilizing the beneficial effects of estrogen for the prevention of osteoar…
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Journal:
Authors:
- Tankó LB,
- Søndergaard BC,
- Oestergaard S,
- Karsdal MA,
- Christiansen C,
Rheumatology, Osteoarthritis
7. Nov 2007
Calcitonin affects both bone and cartilage: a dual action treatment for osteoarthritis?
Osteoarthritis (OA) is the most common form of degenerative joint diseases and a major cause of disability and impaired quality of life in the elderly. OA is a complex disease involving both bone and cartilage properties, and may therefore require alternative approaches for treatment. Recent lines o…
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Journal:
Authors:
- Karsdal MA,
- Sondergaard BC,
- Arnold M,
- Christiansen C,
Rheumatology, Osteoarthritis
14. Oct 2007
Osteoarthritic cartilage is more homogeneous than healthy cartilage: identification of a superior region of interest colocalized with a major risk factor for osteoarthritis
RATIONALE AND OBJECTIVES:
Cartilage loss as determined by magnetic resonance imaging (MRI) or joint space narrowing as determined by x-ray is the result of cartilage erosion. However, metabolic processes within the cartilage that later result in cartilage loss may be a more sensitive assessment met…
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Journal:
Authors:
- Qazi AA,
- Dam EB,
- Nielsen M,
- Karsdal MA,
- Pettersen PC,
- Christiansen C,
Rheumatology, Osteoarthritis
15. Aug 2007
The effect of oral calcitonin on cartilage turnover and surface erosion in an ovariectomized rat model
OBJECTIVE:
To investigate whether oral calcitonin treatment influences the increases in type II collagen (CII) degradation and related surface erosions of articular cartilage in ovariectomized rats.
METHODS:
Fifty rats were randomly allocated into 1 of the 5 following intervention groups: sham-…
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Journal:
Authors:
- Sondergaard BC,
- Oestergaard S,
- Christiansen C,
- Tankó LB,
- Karsdal MA,
Rheumatology, Osteoarthritis
10. Aug 2007
Bone, cartilage and hormone therapy: established concepts and future scenarios
In the aftermath of the Women's Health Initiative (WHI) study, the firm ground of postmenopausal hormone therapy (HT) has been thoroughly shaken. While there was agreement that HT is indicated for the therapy of menopause-associated vasomotor symptoms and vulvovaginal atrophy, there was a general an…
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Journal:
Authors:
- Holinka CF,
- Karsdal MA,
- Christiansen C,
Rheumatology, Osteoarthritis
20. May 2007
Induction of increased cAMP levels in articular chondrocytes blocks matrix metalloproteinase-mediated cartilage degradation, but not aggrecanase-mediated cartilage degradation
OBJECTIVE:
Calcitonin has been suggested to have chondroprotective effects. One signaling pathway of calcitonin is via the second messenger cAMP. We undertook this study to investigate whether increased cAMP levels in chondrocytes would be chondroprotective.
METHODS:
Cartilage degradation was i…
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Journal:
Authors:
- Karsdal MA,
- Sumer EU,
- Wulf H,
- Madsen SH,
- Christiansen C,
- Fosang AJ,
- Sondergaard BC,
Rheumatology, Osteoarthritis
10. May 2007
Separation of healthy and early osteoarthritis by automatic quantification of cartilage homogeneity
OBJECTIVE:
Cartilage loss as determined either by magnetic resonance imaging (MRI) or by joint space narrowing in X-rays is the result of cartilage erosion. However, metabolic processes within the cartilage that later result in cartilage loss may be a more accurate assessment method for early chang…
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Journal:
Authors:
- Qazi AA,
- Folkesson J,
- Karsdal MA,
- Christiansen C,
- Dam EB,
Rheumatology, Osteoarthritis
15. Mar 2007
Anabolic and catabolic function of chondrocyte ex vivo is reflected by the metabolic processing of type II collagen
The aim of the present study was to investigate collagen metabolism after anabolic and catabolic stimulation of chondrocytes ex vivo.
DESIGN:
Metabolic activities in ex vivo bovine cartilage explants were stimulated with insulin-like growth factor I (IGF-I) or a combination of tumor necrosis fac…
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Journal:
Authors:
- Olsen AK,
- Sondergaard BC,
- Byrjalsen I,
- Tankó LB,
- Christiansen C,
- Müller A,
- Hein GE,
- Karsdal MA,
- Qvist P,
Rheumatology, Osteoarthritis
15. Feb 2007
MMP and non-MMP-mediated release of aggrecan and its fragments from articular cartilage: a comparative study of three different aggrecan and glycosaminoglycan assays
Aggrecan is the major proteoglycan in articular cartilage and is known to be degraded by various proteases, including matrix metalloproteinases (MMPs). The present study was undertaken to develop immunoassays detecting aggrecan and its fragments generated by MMP and non-MMP-mediated proteolysis.
…
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Journal:
Authors:
- Sumer EU,
- Sondergaard BC,
- Rousseau JC,
- Delmas PD,
- Fosang AJ,
- Karsdal MA,
- Christiansen C,
- Qvist P,
Rheumatology, Osteoarthritis
14. Aug 2006
Calcitonin directly attenuates collagen type II degradation by inhibition of matrix metalloproteinase expression and activity in articular chondrocytes
OBJECTIVE:
Calcitonin was recently reported to counter progression of cartilage degradation in an experimental model of osteoarthritis, and the effects were primarily suggested to be mediated by inhibition of subchondral bone resorption. We investigated direct effects of calcitonin on chondrocytes …
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Journal:
Authors:
- Sondergaard BC,
- Wulf H,
- Henriksen K,
- Schaller S,
- Oestergaard S,
- Qvist P,
- Tankó LB,
- Bagger YZ,
- Christiansen C,
- Karsdal MA,
Rheumatology, Osteoarthritis
3. Aug 2006
Effects of ovariectomy and estrogen therapy on type II collagen degradation and structural integrity of articular cartilage in rats: implications of the time of initiation
OBJECTIVE:
To investigate how the time of initiation influences the effects of estrogen therapy on type II collagen (CII) turnover and the structural integrity of articular cartilage in ovariectomized rats and to determine whether estrogen exerts direct effects on the catabolic function of chondroc…
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Journal:
Authors:
- Oestergaard S,
- Sondergaard BC,
- Hoegh-Andersen P,
- Henriksen K,
- Qvist P,
- Christiansen C,
- Tankó LB,
- Karsdal MA,
Rheumatology, Osteoarthritis
14. Jul 2006
Calcitonin is involved in cartilage homeostasis: is calcitonin a treatment for OA?
OBJECTIVE:
Osteoarthritis (OA) is the most common form of degenerative joint diseases and a major cause of disability and impaired quality of life in the elderly. Recent observations suggest that calcitonin may act on both osteoclasts and chondrocytes. The present review was sought to summarize eme…
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Journal:
Authors:
- Karsdal MA,
- Tankó LB,
- Riis BJ,
- Sondergaard BC,
- Henriksen K,
- Altman RD,
- Qvist P,
- Christiansen C,
Rheumatology, Osteoarthritis
14. Jul 2006
The utility of measuring C-terminal telopeptides of collagen type II (CTX-II) in serum and synovial fluid samples for estimation of articular cartilage status in experimental models of destructive joint diseases
OBJECTIVE:
To characterize and validate a novel, enzyme-linked immunoassay for measuring cross-linked dimer forms of C-terminal telopeptides of type II collagen (CTX-II) in serum and synovial fluid of rodents, and investigate whether CTX-II measurements can reflect joint status in two established a…
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Journal:
Authors:
- Oestergaard S,
- Chouinard L,
- Doyle N,
- Karsdal MA,
- Smith SY,
- Qvist P,
- Tankó LB,
Rheumatology, Osteoarthritis
23. Mar 2006
Relative contribution of matrix metalloprotease and cysteine protease activities to cytokine-stimulated articular cartilage degradation
OBJECTIVE:
Both matrix metalloprotease (MMP) activity and cathepsin K (CK) activity have been implicated in cartilage turnover. We investigated the relative contribution of MMP activity and CK activity in cartilage degradation using ex vivo and in vivo models.
METHODS:
Bovine articular cartilag…
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Journal:
Authors:
- Søndergaard BC,
- Henriksen K,
- Wulf H,
- Oestergaard S,
- Schurigt U,
- Bräuer R,
- Danielsen I,
- Christiansen C,
- Qvist P,
- Karsdal MA,
Rheumatology, Osteoarthritis
7. Jul 2005
Oral salmon calcitonin induced suppression of urinary collagen type II degradation in postmenopausal women: a new potential treatment of osteoarthritis
OBJECTIVE:
To assess the efficacy of 3 months of oral salmon calcitonin (sCT) on cartilage degradation as estimated by the changes in the urinary excretion of C-terminal telopeptide of collagen type II (CTX-II), and to investigate whether the response of oral sCT to urinary CTX-II depends on the ba…
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Journal:
Authors:
- Bagger YZ,
- Tankó LB,
- Alexandersen P,
- Karsdal MA,
- Olson M,
- Mindeholm L,
- Azria M,
- Christiansen C,
Rheumatology, Osteoarthritis
1. Jul 2005
The clinical potential of estrogen for the prevention of osteoarthritis: what is known and what needs to be done?
Osteoarthritis (OA) remains a major epidemiological problem worldwide. The lack of established chondroprotective agents limits the clinical management of this disease to relief of symptoms, such as pain and joint stiffness. The marked increase in the prevalence and incidence of OA among women after …
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Journal:
Authors:
- Tankó LB,
- Karsdal MA,
- Christiansen C,
Rheumatology, Spondyloarthropathies
18. Jan 2002
Matrix metalloproteinase inhibitor BB-3103 unlike the serine proteinase inhibitor aprotinin abrogates epidermal healing of human skin wounds ex vivo
Several matrix metalloproteinases and serine proteinases are upregulated in migrating keratinocytes during cutaneous wound repair. Single cell culture studies indicate the necessity for matrix metalloproteinases but not for serine proteinases in keratinocyte locomotion. To account for epithelial-mes…
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Journal:
Authors:
- Mirastschijski U,
- Impola U,
- Karsdal MA,
- Saarialho-Kere U,
- Agren MS,