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

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


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.

Keywords: Biomarker; Cytokines; Distraction; Orthopaedic; Osteoarthritis; Synovial fluid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*
  • Osteoarthritis, Knee / surgery*
  • Synovial Fluid / metabolism*
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Transforming Growth Factor beta1 / metabolism
  • Treatment Outcome


  • CCL2 protein, human
  • CXCL8 protein, human
  • Cell Adhesion Molecules
  • Chemokine CCL2
  • IL6 protein, human
  • Interleukin-6
  • Interleukin-8
  • LTBP2 protein, human
  • Latent TGF-beta Binding Proteins
  • TGFB1 protein, human
  • TIMP1 protein, human
  • TNFAIP6 protein, human
  • Tissue Inhibitor of Metalloproteinase-1
  • Transforming Growth Factor beta1
  • activin A
  • Fibroblast Growth Factor 2
  • Activins
  • MMP3 protein, human
  • Matrix Metalloproteinase 3