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[The Effects of NF-kappaB Signalling on the TNF-α induced Ratios of MMPs to TIMPs in Chondrocytes].
Sichuan da Xue Xue Bao. Yi Xue Ban = Journal of Sichuan University. Medical Science Edition 2016 September
OBJECTIVES: To explore the influence of the NF-κB inhibitor (bay11-7082) on tumor necrosis factor-α (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 MMPs and TIMPs in 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 MMPs and TIMPs ( P <0.05). The ratios of MMPs/TIMPs were mostly increased except the part of MMP -1. Bay11-7082 could reduce TNF-α-induced MMPs and TIMPs gene expressions, and could make the increased ratio of MMPs/TIMPs dropped to the normal level of chondrocytes. Similar results were observed at the protein level of the gelatinases by zymography.
CONCLUSIONS: 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.
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 MMPs and TIMPs in 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 MMPs and TIMPs ( P <0.05). The ratios of MMPs/TIMPs were mostly increased except the part of MMP -1. Bay11-7082 could reduce TNF-α-induced MMPs and TIMPs gene expressions, and could make the increased ratio of MMPs/TIMPs dropped to the normal level of chondrocytes. Similar results were observed at the protein level of the gelatinases by zymography.
CONCLUSIONS: 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.
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