Metformin Attenuates Monosodium-Iodoacetate-Induced Osteoarthritis via Regulation of Pain Mediators and the Autophagy–Lysosomal Pathway

• Main Authors: Hyun Sik Na, Ji Ye Kwon, Seon-Yeong Lee, Seung Hoon Lee, A Ram Lee, Jin Seok Woo, KyungAh Jung, Keun-Hyung Cho, Jeong-Won Choi, Dong Hwan Lee, Hong-Ki Min, Sung-Hwan Park, Seok Jung Kim, Mi-La Cho
• Format: Article
• Language: English
• Published: MDPI AG 2021-03-01
• Series: Cells
• Subjects: osteoarthritis; metformin; pain; cartilage; autophagy; combination therapy
• Online Access: https://www.mdpi.com/2073-4409/10/3/681

Osteoarthritis (OA) is the most common degenerative arthritis associated with pain and cartilage destruction in the elderly; it is known to be involved in inflammation as well. A drug called celecoxib is commonly used in patients with osteoarthritis to control pain. Metformin is used to treat type 2 diabetes but also exhibits regulation of the autophagy pathway. The purpose of this study is to investigate whether metformin can treat monosodium iodoacetate (MIA)-induced OA in rats. Metformin was administered orally every day to rats with OA. Paw-withdrawal latency and threshold were used to assess pain severity. Cartilage damage and pain mediators in dorsal root ganglia were evaluated by histological analysis and a scoring system. Relative mRNA expression was measured by real-time PCR. Metformin reduced the progression of experimental OA and showed both antinociceptive properties and cartilage protection. The combined administration of metformin and celecoxib controlled cartilage damage more effectively than metformin alone. In chondrocytes from OA patients, metformin reduced catabolic factor gene expression and inflammatory cell death factor expression, increased LC3Ⅱb, p62, and LAMP1 expression, and induced an autophagy–lysosome fusion phenotype. We investigated if metformin treatment reduces cartilage damage and inflammatory cell death of chondrocytes. The results suggest the potential for the therapeutic use of metformin in OA patients based on its ability to suppress pain and protect cartilage.