Effects of Hyaluronan on the Production of Stromelysin and Tissue Inhibitor of Metalloproteinase-1 (Timp-1) in Bovine Articular Chondrocytes

On exposing isolated bovine articular chondrocytes to hyaluronan (HA) for 2, 5 and 7 days at 0.25 to 1.0 mg/ml, HA with a high molecular weight (M,) (2.0 >< 106) stimulated the production of tissue inhibitor of metalloproteinase-1 (TIMP-1) in an exposure-time-dependent manner.In the presence of 100 U/ml interleukin-la (IL-la), a condition that reduced TIMPl production but increased prostromelysin production, HA with M, of 0.5 >< 106, 1.0 >< 106 and 2.0 >< 106 at 0.5 mg/ml significantly enhanced the TIMP-1 production in the media in a M,dependent manner after 2, 4 and 8 days of incubation.However, HA increased stromelysin activity in an inconsistent and non-M,-dependent manner.Stromelysin/TIMP-1 ratio was reduced by HA in a M,-dependent manner, suggesting that HA serves as a protective component for cartilage degradation by increasing the TIMP-1 production.