The Effects of NF-kappa B Signalling on the TNF-alpha-induced Ratios of MMPs to TIMPs in Chondrocytes

Objective To explore the influence of the NF-κB inhibitor (bay11-7082) on tumor necrosis factor-alpha (TNF-α)-induced different ratios of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in chondrocytes. Methods Chondrocytes were isolated from the knee joint of a 1-day old mouse by trypsin digestion method. Hematoxylin-Eosin (HE) stain was used to show the morphology of isolated chondrocytes; Semi-quantitative PCR was applied to analyze the influence of bay11-7082 on gene expressions of TNF-α-induced MMPsand TIMPsin chondrocytes; Zymography was used to elucidate activities of the gelatinases induced by TNF-α and/or bay11-7082. Results TNF-α up-regulated gene expressiosn of the MMPsand TIMPs(P<0.05). The ratios of MMPs/TIMPswere mostly increased except the part of MMP-1. Bay11-7082 could reduce TNF-α-induced MMPsand TIMPsgene expressions, and could make the increased ratio of MMPs/TIMPsdropped to the normal level of chondrocytes. Similar results were observed at the protein level of the gelatinases by zymography. Conclusion TNF-α-induced high ratios of MMPs/TIMPs could partiallyexplain over-degradation of cartilage extracellular matrix in osteoarthritis (OA). Blockage of NF-κB with bay11-7082 might provide a possible therapeutic strategy for the OA deterioration.