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

Abstract

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 ^INK4a 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-1β-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.