The molecular profile of synovial fluid changes upon joint distraction and is associated with clinical response in knee osteoarthritis
Watt, F. E.; Hamid, B.; Garriga, C.; Judge, A.; Hrusecka, R.; Custers, R. J.H.; Jansen, M. P.; Lafeber, F. P.; Mastbergen, S. C.; Vincent, T. L.
(2020) Osteoarthritis and Cartilage, volume 28, issue 3, pp. 324 - 333
(Article)
Abstract
OBJECTIVE: Surgical knee joint distraction (KJD) leads to clinical improvement in knee osteoarthritis (OA) and also apparent cartilage regeneration by magnetic resonance imaging. We investigated if alteration of the joint's mechanical environment during the 6 week period of KJD was associated with a molecular response in synovial fluid, and if
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any change was associated with clinical response. METHOD: 20 individuals undergoing KJD for symptomatic radiographic knee OA had SF sampled at baseline, midpoint and endpoint of distraction (6 weeks). SF supernatants were measured by immunoassay for 10 predefined mechanosensitive molecules identified in our previous pre-clinical studies. The composite Knee injury and OA Outcome Score-4 (KOOS 4) was collected at baseline, 3, 6 and 12 months. RESULTS: 13/20 (65%) were male with mean age 54°±°5yrs. All had Kellgren-Lawrence grade ≥2 knee OA. 6/10 analytes showed statistically significant change in SF over the 6 weeks distraction (activin A; TGFβ-1; MCP-1; IL-6; FGF-2; LTBP2), P < 0.05. Of these, all but activin A increased. Those achieving the minimum clinically important difference of 10 points for KOOS 4 over 6 months showed greater increases in FGF-2 and TGFβ-1 than non-responders. An increase in IL-8 during the 6 weeks of KJD was associated with significantly greater improvement in KOOS 4 over 12 months. CONCLUSION: Detectable, significant molecular changes are observed in SF following KJD, that are remarkably consistent between individuals. Preliminary findings appear to suggest that increases in some molecules are associated with clinically meaningful responses. Joint distraction may provide a potential opportunity in the future to define regenerative biomarker(s) and identify pathways that drive intrinsic cartilage repair.
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Keywords: Activins/metabolism, Cell Adhesion Molecules/metabolism, Chemokine CCL2/metabolism, External Fixators, Female, Fibroblast Growth Factor 2/metabolism, Humans, Interleukin-6/metabolism, Interleukin-8/metabolism, Latent TGF-beta Binding Proteins/metabolism, Male, Matrix Metalloproteinase 3/metabolism, Middle Aged, Orthopedic Procedures/methods, Osteoarthritis, Knee/metabolism, Synovial Fluid/metabolism, Tissue Inhibitor of Metalloproteinase-1/metabolism, Transforming Growth Factor beta1/metabolism, Treatment Outcome, Biomedical Engineering, Rheumatology, Orthopedics and Sports Medicine, Research Support, Non-U.S. Gov't, Journal Article
ISSN: 1063-4584
Publisher: W.B. Saunders Ltd
Note: Funding Information: This work was supported by coordinated project grants from Versus Arthritis project grant ( 20783 ), Centre for OA Pathogenesis Versus Arthritis (grants 20205 and 21621 ) and the Kennedy Trust for Rheumatology Research (all of the UK), and also ReumaNederland, the Dutch Arthritis Society ( ISP14-3-301/16-1-404 ) for the work in the UK and The Netherlands for the study respectively. FEW is supported by a UKRI Future Leaders Fellowship and was supported during this work in part by the NIHR Oxford Biomedical Research Centre . The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The study funders/study sponsors had no involvement in the study design, data collection, analysis or interpretation of the study, or in the writing of, or decision to submit the manuscript. Funding Information: Fiona Watt: no conflicts of interest; other unrelated funding received from Pfizer Ltd , USA clinical study ( AZR00860 ) and from Astellas European Foundation clinical study ( AZR00850 ). Benjamin Hamid: no conflicts of interest. Cesar Garriga: no conflicts of interest. Andrew Judge: no conflicts of interest. Renata Hrusecka: no conflicts of interest. Roel Custers: no conflicts of interest. Mylene Jansen: no conflicts of interest. Floris Lafeber - is co-founder, shareholder, and co-director of ArthroSave BV, and is consultant for Synerkine Pharma BV, both spin-off companies of the UMC Utrecht involved in treatment of osteoarthritis. Simon Mastbergen: no conflicts of interest. Tonia Vincent: no conflicts of interest. Funding Information: Fiona Watt: no conflicts of interest; other unrelated funding received from Pfizer Ltd, USA clinical study (AZR00860) and from Astellas European Foundation clinical study (AZR00850).This work was supported by coordinated project grants from Versus Arthritis project grant (20783), Centre for OA Pathogenesis Versus Arthritis (grants 20205 and 21621) and the Kennedy Trust for Rheumatology Research (all of the UK), and also ReumaNederland, the Dutch Arthritis Society (ISP14-3-301/16-1-404) for the work in the UK and The Netherlands for the study respectively. FEW is supported by a UKRI Future Leaders Fellowship and was supported during this work in part by the NIHR Oxford Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. Publisher Copyright: © 2020 The Authors
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