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…

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…

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…

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)…

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…

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…

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…

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…

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…

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…

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…

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…

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…

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…

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…

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…

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…

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…

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…

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…

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 …

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…

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…

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…

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…

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…

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…

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…

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…

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, …

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…

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 …

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…

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…

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. …

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…

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…

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…

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…

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…

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 …

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…

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 …

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…

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…

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…

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…

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…

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…

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…

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…

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…

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…

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…

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…

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…

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…

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…

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…

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 …

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…

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…

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) …

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…

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…

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…

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…

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…

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…

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…

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…

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…

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…

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…

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…

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…

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…