Metformin protects osteoarthritis in mice by regulating the AMPK signaling pathways
TAN Qing-mei, YANG Cheng, LIAO Jian-wen, Zou Qingbao， Huang Aijun， LIN Li, ZHANG Cong-xin
Chinese Journal of Clinical Anatomy ›› 2017, Vol. 35 ›› Issue (4) : 413-418.
Metformin protects osteoarthritis in mice by regulating the AMPK signaling pathways
Objective Study the effect of metformin on osteoarthritis and chondrocyte differentiation in mice. Methods Mice were divided into a control group and an experimental group whose anterior cruciate ligament and medial meniscus excision were done in the right knee of both groups for arthritis model; Aftersuccess of model establishment, the experimental group was given metformin (2mg/kg/d) and the control group was given saline as intervention treatment for 8 weeks; Then through the HE, sarranine O-fast green slice staining and Micro-CT structural change was observed and grading was performed according to Mankin ratings; The AMPK, mTOR activity and degree of autophagy of articular cartilage in two groups were tested by Western Blot; Chondrocytes were cultivated in vitro and stimulated by metformin to observe the cell morphology, and amount. The cell activity was determined by MTT method .The cell activity of AMPK, mTOR and autophagy were detected by Western Blot. Results (1)We succeeded in establishing the model of osteoarthritis in mice and found metformin could protect the osteoarthritis by Micro - CT, HE and sarranine O-fast green slice staining and Mankin ratings. (2) Western Blot results showed metformin activated AMPK and enhanced autophagy to protect osteoarthritis. (3) MTT method showed metformin inhibited Chondrocytes differentiation,and Western Blot results showed metformin promoted chondrocytes autophagy. Conclusions Metformin activates AMPK signaling pathways, inhibits mTOR signaling pathways, protecting chondrocyte autophagy，thus protects osteoarthritis in mice.
Metformin; / Osteoarthritis; / AMPK; / mTOR; / Autophagy
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