Figure 2. Metformin reduces the degradation of cartilage matrix and stimulates its synthesis, while also affecting the formation of osteophytes. (A) Immunohistochemical detection of MMP-13 in tibial cartilage at 2, 5, and 10 weeks after destabilization of the medial meniscus surgery. (B) Quantification of cells positively stained for matrix metalloproteinase-13 (MMP-13). (C) The mRNA expression levels of MMP-13, SOX9, COLX and COL2al, and (D) Western blot analyses of the protein expression levels of MMP-13 and COL2al. Primary chondrocytes were induced with IL-1β (10 ng/mL), and then co-cultured with metformin (1, 2, 4, and 5 mM) for 72 h. Two important cartilage matrix degrading proteins, MMP-13 and COLX, were decreased during administration, while other important cartilage matrix synthetic proteins, SOX9 and COL2al, were promoted during administration at 72 h. *P < 0.05; **P < 0.01; ***P < 0.001 between two groups.