MMP protein and activity levels in synovial fluid from patients with joint injury, inflammatory arthritis, and osteoarthritis

Abstract

Objective: To determine protein and activity levels of matrix metalloproteinases 1 and 3 (MMP-1 and MMP-3) in synovial fluid of patients with knee joint injury, primary osteoarthritis, and acute pyrophosphate arthritis (pseudogout).

Methods: Measurements were done on knee synovial fluid obtained in a cross sectional study of cases of injury (n = 283), osteoarthritis (n = 105), and pseudogout (n = 65), and in healthy controls (n = 35). Activity of MMP-1 and MMP-3 in alpha(2) macroglobulin complexes was measured using specific low molecular weight fluorogenic substrates. ProMMP-1, proMMP-3, and TIMP-1 (tissue inhibitor of metalloproteinase 1) were quantified by immunoassay.

Results: Mean levels of proMMP-1, proMMP-3, and TIMP-1 were increased in injury, osteoarthritis, and pseudogout compared with controls. MMP-1 activity was increased in pseudogout and injury groups over control levels, whereas MMP-3 activity was increased only in the pseudogout group. The increase in MMP-1 activity coincided with a decrease in TIMP-1 levels in the injury group.

Conclusions: Patients with joint injury have a persistent increase in proMMP-1 and proMMP-3 in synovial fluid and an increase in activated MMPs, which are not inhibited by TIMP. The differences in activation and inhibition patterns between the study groups are consistent with disease specific patterns of MMP activation and/or inhibition in joint pathology.

Figures

Figure 1

ProMMP-1 concentration (A), MMP-1 activity (B), TIMP-1 concentration (C), proMMP-3 concentration (D), and MMP-3 activity (E) in synovial fluid v time after injury (values are medians with standard errors). The whole group was divided into "time windows" based on time of sampling after injury: 0–0.6 weeks (n = 44), 0.6–2 weeks (n = 58), 2–17 weeks (n = 45), 17–57 weeks (n = 50), 58–170 weeks (n = 47), 180–1500 weeks (n = 39). Time of sampling after injury is reported on a logarithmic scale. Dashed line represents corresponding values in control groups. MMP, matrix metalloproteinase; proMMP, pro-matrix metalloproteinase; TIMP, tissue inhibitor of metalloproteinases.

Figure 2

ProMMP-1 concentration (A), MMP-1 activity (B), TIMP-1 concentration (C), proMMP-3 concentration (D), and MMP-3 activity (E) in synovial fluid of the study groups (values are medians with standard error bars). CTRL, knee-healthy controls; INFL, inflammatory arthritis (pseudogout); OA, osteoarthritis. α: pv INFL; ß: p<0.001, CTRL v OA.