Influence of Dexamethasone on Matrix Metalloproteinase Production from Human Synovial Fibroblasts in vitro

The effects of dexamethasone on the production of matrix metal-loproteinase (MMP) by synovial fibroblasts (SFs) were examined in vitro. Cultured SFs originating from patients with osteoarthritis were stimulated with either lipopolysaccharide or transforming growth factor-β (TGF-β) in the presence of various concentrations of dexamethasone. MMP and tissue inhibitor of metalloproteinase (TIMP) concentrations in 24-hour culture supernatants were determined by ELISA. Although lower doses of dexamethasone (10 and 25 μg / mL) did not suppress the production of MMP-1, -2, or -3 in response to lipopolysaccharide stimulation, dexamethasone at concentrations greater than 50 μg / mL significantly suppressed the production of those MMP types. In contrast, dexamethasone did not inhibit TIMP-1 and -2 production by SF, even at a concentration of 250 μg / mL. Dexamethasone also did not inhibit the production of MMPs and TIMPs by SF stimulated with TGF-β. These results suggest that dexamethasone suppresses the production of MMPs by inhibiting signaling pathways that are activated by inflammatory stimulation. These findings also indicate that the suppressive activity of dexamethasone on MMP production may be partially responsible for the favorable effect of this drug on the clinical status of inflammatory diseases of the knee such as osteoarthritis.