Synovitis biomarkers:<i>ex vivo</i>characterization of three biomarkers for identification of inflammatory osteoarthritis

Kjelgaard-Petersen, Cecilie Freja; Siebuhr, Anne Sofie; Christiansen, T.; Ladel, Christoph; Karsdal, Morten A.; Bay‐Jensen, Anne‐Christine

doi:10.3109/1354750x.2015.1105497

Cited by 35 publications

(23 citation statements)

References 38 publications

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“…In support of this, both markers were increased in the conditioned media of OA synovial explants after treatment with the cytokines TNFα or IL-1β 13 . The finding that the change in IL-6 was associated with the change in both markers in the present study also suggests that these markers are responsive to a change in an inflammatory process.…”

Section: Discussionmentioning

confidence: 54%

“…The C1M, C2M and C3M biomarkers recognize neoepitopes in types I, II, and III collagen, respectively, that are generated by MMP cleavage of collagen in the soft connective tissues (C1M and C3M) including synovium, tendons and ligaments but not in bone and the articular cartilage (C2M) 12, 13 . The CRPM biomarker recognizes a fragment of CRP and is thought to be a marker of chronic inflammation in OA 12 .…”

Section: Resultsmentioning

confidence: 99%

“…For this study, which represents a secondary analysis of the IDEA trial, markers of MMP-mediated degradation of type I (C1M), type II (C2M), and type III (C3M) collagen were measured, as well as a marker of C-reactive protein (CRP) degradation (CRPM). These markers have been suggested to measure inflammation-mediated tissue destruction including that caused by synovitis 12, 13 .…”

Section: Introductionmentioning

confidence: 99%

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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)

Loeser

Beavers

Bay‐Jensen

et al. 2017

Osteoarthritis and Cartilage

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Summary 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 OA. Design Blood samples were analyzed from 429 participants in the IDEA trial randomized to either an 18 month exericse control group (E), weight loss diet (D), or D+E. C1M, C2M, C3M and CRPM biomarkers and IL-6 were quantitated using ELISAs. Radiographic progression was defined as a decrease in joint space width of ≥ 0.7mm. Statistical modeling of group means and associations used mixed models adjusted for visit, baseline BMI, gender, and baseline values of the outcome. Results Compared to the E control group, C1M was significantly lower in the D and D+E groups at both 6 and 18 months while C3M was significantly lower in D and D+E at 6 months and in D+E at 18 months. C2M did not change in any group. Using data from all groups, change in C1M (p<0.0001), C3M (p<0.0001), as well as CRPM (p=0.0004) from baseline to 18 months was positively associated with change in weight. No marker was associated with change in WOMAC pain or radiographic progression. C3M (p=0.008) and CRPM (p=0.028) were positively associated with change in WOMAC function. Change in IL-6 was positively associated with change in C1M, C3M, and CRPM. Conclusion Overweight and obese adults with knee OA who lost weight from diet and diet plus exercise reduced serum markers of interstitial matrix turnover and inflammation but not type II collagen degradation.

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Section: Discussionmentioning

confidence: 54%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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)

Loeser

Beavers

Bay‐Jensen

et al. 2017

Osteoarthritis and Cartilage

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“…Kjelgaard-Petersen and colleagues primary treated fibroblast-like synoviocytes and synovial membrane explants (SMEs) with various pro-inflammatory cytokines and growth factors and assessed the biological activity of the proteases in this model using C1M, C3M, and active MMP-3 assays in the conditioned medium from the cells and explants. Their work suggests that C1M, C3M, and active MMP-3 may be used as biomarkers of synovitis in ex vivo models and provides a novel translational tool for synovitis 75 .…”

Section: Proteomics Novel Oa Biomarkers New Biomarker Assays and Mamentioning

confidence: 99%

Osteoarthritis Year in Review 2016: biomarkers (biochemical markers)

Mobasheri

Bay‐Jensen

Spil

et al. 2017

Osteoarthritis and Cartilage

127

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There has been steady progress in osteoarthritis (OA) biomarker research in 2016. Several novel biomarkers were identified and new technologies have been developed for measuring existing biomarkers. However, there has been no "quantum leap" this past year and identification of novel early OA biomarkers remains challenging. During the past year, OARSI published a set of recommendations for the use of soluble biomarkers in clinical trials, which is a major step forward in the clinical use of OA biomarkers and bodes well for future OA biomarker development.

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“…They serve as biomarkers of interstitial membrane inflammation 30, 31. We have previously shown that C1M and C3M are up‐regulated in RA, osteoarthritis (OA), spondyloarthritis, and ex vivo in synovial membrane explants in response to TNF 24, 32, 33, 34, 35, 36. Importantly for the context of this study, C1M has been shown to be prognostic for disease progression in RA 33 and C1M and C3M levels are correlated with disease activity 37, 38, emphasizing the significance of interstitial tissue inflammation for progression of disease.…”

mentioning

confidence: 99%

Translational Biomarkers and Ex Vivo Models of Joint Tissues as a Tool for Drug Development in Rheumatoid Arthritis

Kjelgaard-Petersen

Platt

Braddock

et al. 2018

Arthritis & Rheumatology

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ObjectiveRheumatoid arthritis (RA) is a chronic and degenerative autoimmune joint disease that leads to disability, reduced quality of life, and increased mortality. Although several synthetic and biologic disease‐modifying antirheumatic drugs are available, there is still a medical need for novel drugs that control disease progression. As only 10% of experimental drug candidates for treatment of RA that enter phase I trials are eventually registered by the Food and Drug Administration, there is an immediate need for translational tools to facilitate early decision‐making in drug development. In this study, we aimed to determine if the inability of fostamatinib (a small molecule inhibitor of Syk) to demonstrate sufficient efficacy in phase III of a previous clinical study could have been predicted earlier in the development process.MethodsBiomarkers of bone, cartilage, and interstitial matrix turnover (C‐telopeptide of type I collagen [CTX‐I], matrix metalloproteinase–derived types I, II, and III collagen neoepitopes [C1M, C2M, and C3M]) were measured in 450 serum samples from the Oral Syk Inhibition in Rheumatoid Arthritis 1 study (OSKIRA‐1, a phase III clinical study of the efficacy of fostamatinib in RA) at baseline and follow‐up. Additionally, the same biomarkers were subsequently measured in conditioned media from osteoclast, cartilage, and synovial membrane cultured with the active metabolite of fostamatinib, R406, to assess the level of suppression induced by the drug.ResultsIn OSKIRA‐1 serum samples and osteoclast and cartilage cultures, fostamatinib suppressed the levels of CTX‐I and C2M. In OSKIRA‐1 serum samples and synovial membrane cultures, fostamatinib did not mediate any clinical or preclinical effect on either C1M or C3M, which have previously been associated with disease response and efficacy.ConclusionThese data demonstrate that translational biomarkers are a potential tool for early assessment and decision‐making in drug development for RA treatment.

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Synovitis biomarkers:ex vivocharacterization of three biomarkers for identification of inflammatory osteoarthritis

Cited by 35 publications

References 38 publications

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)

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)

Osteoarthritis Year in Review 2016: biomarkers (biochemical markers)

Translational Biomarkers and Ex Vivo Models of Joint Tissues as a Tool for Drug Development in Rheumatoid Arthritis

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