Metformin attenuates cartilage degeneration in an experimental osteoarthritis model by regulating AMPK/mTOR

Background: It is generally thought that the occurrence and progression of osteoarthritis (OA) results from multiple causes, including degradation and destruction of the cartilage matrix and aging of chondrocytes. Metformin is a first-line drug for the treatment of diabetes, and has great potential for the treatment of other disorders. However, the role of metformin in OA is unknown. Results: Metformin displayed a protective effect against OA. There were lower OARSI scores and fewer MMP-13-positive cells in DMM mice and cartilage explants after treatment with metformin. In addition, metformin treatment decreased p16(INK4)(a) levels in OA chondrocytes, and enhanced polarization of AMPK and inhibition of mTORC1 in OA mice and chondrocytes in a dose-dependent manner. Conclusions: Metformin effectively alleviated cartilage degradation and aging through regulation of the AMPK/mTOR signaling pathways, suggesting that it could be an effective treatment for OA. Methods: The effects of metformin on cartilage degradation and chondrocyte aging was determined in a destabilization of the medial meniscus (DMM)-induced OA mouse model and in IL-1 beta-treated mouse chondrocytes and cartilage explants. Articular cartilage degeneration was graded using the Osteoarthritis Research Society International (OARSI) criteria. Immunostaining, RT-PCR, and western blot analyses were conducted to detect the relative expressions of protein and RNA.