Titanium particles up-regulate the activity of matrix metalloproteinase-2 in human synovial cells

Purpose

Wear debris particle-induced osteolysis and subsequent aseptic loosening is one of the major causes of failure of total joint replacement. The purpose of this study was to investigate the effect of titanium implant material and inflammatory cytokines on human synovial cells and the development to osteolysis and aseptic loosening.

Methods

This study investigated the effect of titanium implant material on the ECM-degraded MMP-2 in human synovial cells and analyzed the contribution of synovial cells in osteolysis and aseptic loosening.

Results

When human synovial cells are exposed to titanium materials, MMP-2 activity is induced by 1.72 ± 0.14-fold with Ti disc and 3.95 ± 0.10-fold with Ti particles, compared with that of the controls, respectively. Inflammatory cytokines TNFα and IL-1β are also shown to induce MMP-2 activity by 3.65 ± 0.28-fold and 6.76 ± 0.28-fold, respectively. A combination of Ti particles and cytokines induces MMP-2 activities to a higher level (10.54 ± 0.45-fold). Inhibitors of various signal pathways involved in MMP-2 reverse Ti particle-induced MMP-2 activities.

Conclusions

Synovial cells surrounding the bone–prosthesis interface may contribute to production of MMP-2, and NFκB inhibitors may be explored as potential therapeutics to alleviate wear debris-induced osteolysis and aseptic loosening.