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The molecular profile of synovial fluid changes upon joint distraction and is associated with clinical response in knee osteoarthritis

Author

Osteoarthritis Cartilage. 2020 Mar;28(3):324-333. doi: 10.1016/j.joca.2019.12.005.Epub 2020 Jan 2.

F E Watt 1B Hamid 2C Garriga 3A Judge 4R Hrusecka 5R J H Custers 6M P Jansen 7F P Lafeber 8S C Mastbergen 9T L Vincent 10

Author Information

1 Centre for Osteoarthritis Pathogenesis Versus Arthritis, Kennedy Institute of Rheumatology, Roosevelt Drive, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, UK. Electronic address: fiona.watt@kennedy.ox.ac.uk.

2 Centre for Osteoarthritis Pathogenesis Versus Arthritis, Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, UK. Electronic address: benjamin.hamid@fu-berlin.de.

3 Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, UK. Electronic address: cesar.garriga@phc.ox.ac.uk.

4 Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, UK; Musculoskeletal Research Unit, University of Bristol, UK; National Institute for Health Research Bristol Biomedical Research Centre (NIHR Bristol BRC), University Hospitals Bristol NHS Foundation Trust, UK; MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, UK. Electronic address: andrew.judge@ndorms.ox.ac.uk.

5 Centre for Osteoarthritis Pathogenesis Versus Arthritis, Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, UK. Electronic address: rhrusecka@googlemail.com.

6 Department of Orthopaedic Surgery, University Medical Center Utrecht, the Netherlands. Electronic address: rcuster2@umcutrecht.nl.

7 Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, the Netherlands. Electronic address: M.P.Jansen-36@umcutrecht.nl.

8 Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, the Netherlands. Electronic address: F.Lafeber@umcutrecht.nl.

9 Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, the Netherlands. Electronic address: s.mastbergen@umcutrecht.nl.

10 Centre for Osteoarthritis Pathogenesis Versus Arthritis, Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, UK. Electronic address: tonia.vincent@kennedy.ox.ac.uk.

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 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 (KOOS4) 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 KOOS4 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 KOOS4 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.