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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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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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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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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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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
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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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, 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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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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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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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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Authors:

  • Sanchez C,
  • Bay-Jensen AC,
  • Pap T,
  • Dvir-Ginzberg M,
  • Quasnichka H,
  • Barrett-Jolley R,
  • Mobasheri A,
  • Henrotin Y,
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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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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Authors:

  • Mobasheri A,
  • Bay-Jensen AC,
  • Van Spil WE,
  • Larkin J,
  • Levesque MC,
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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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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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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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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Authors:

  • Kraus VB,
  • Blanco FJ,
  • Englund M,
  • Karsdal MA,
  • Lohmander LS,
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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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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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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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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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,
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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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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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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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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Bone
18. Feb 2010

The effect of oral salmon calcitonin delivered with 5-CNAC on bone and cartilage degradation in osteoarthritic patients: a 14-day randomized study

BACKGROUND:
The aim of this study was to investigate the pharmacokinetic and pharmacodynamic parameters of oral salmon calcitonin (oSCT) administered over 14 days to men and women presenting with osteoarthritis (OA).

MATERIALS AND METHODS:
The study was a phase-I, 2-week, placebo-controlled, do…

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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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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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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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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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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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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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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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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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