Decreased lubricin concentrations and markers of joint inflammation in the synovial fluid of patients with anterior cruciate ligament injury

Arthritis Rheum. 2008 Jun;58(6):1707-15. doi: 10.1002/art.23495.


Objective: To study the effect of anterior cruciate ligament (ACL) injury on lubricin concentrations in synovial fluid (SF) and its correlation with time postinjury, inflammatory cytokines, lubricin-degrading enzymes, and SF proteoglycan content.

Methods: SF samples were obtained from both knees of 30 patients with unilateral ACL insufficiency, 32-364 days postinjury. Lubricin, inflammatory cytokines (interleukin-1beta [IL-1beta], tumor necrosis factor alpha [TNFalpha], and IL-6), and catabolic enzymes (procathepsin B and neutrophil elastase) were measured in SF from injured and contralateral (uninjured) joints, by enzyme-linked immunosorbent assay. Sulfated glycosaminoglycan (sGAG) levels in the SF were measured by Alcian blue binding assay.

Results: SF lubricin concentrations were significantly (P < 0.001) reduced at an early stage following ACL injury when compared with those in the contralateral joint. Within 12 months, the lubricin concentration in the injured knee (slope = 0.006, SE = 0.00010, P < 0.001) approached that in the contralateral knee, which did not change with time (slope = -0.0002, SE = 0.00050, P = 0.71). TNFalpha levels showed a significant negative relationship with log2 lubricin levels. IL-1beta, TNFalpha, IL-6, procathepsin B, and neutrophil elastase concentrations in SF from injured knees were greater in samples from recently injured knees compared with those that were chronically injured. There were no detectable cytokines or enzymes in the SF of contralateral joints. Concentrations of sGAG were significantly (P = 0.0002) higher in the SF from injured knees compared with the contralateral joints.

Conclusion: The decrease in SF lubricin concentrations following ACL injury may place the joint at an increased risk of wear-induced damage as a consequence of lack of boundary lubrication, potentially leading to secondary osteoarthritis. The decrease in SF lubricin was associated with an increase in levels of inflammatory cytokines.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Anterior Cruciate Ligament Injuries*
  • Cathepsin B / metabolism
  • Cohort Studies
  • Enzyme Precursors / metabolism
  • Female
  • Glycoproteins / metabolism*
  • Humans
  • Interleukin-6 / metabolism
  • Leukocyte Elastase / metabolism
  • Male
  • Middle Aged
  • Synovial Fluid / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism


  • Enzyme Precursors
  • Glycoproteins
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • lubricin
  • Leukocyte Elastase
  • procathepsin B
  • Cathepsin B