Curcumin monoglucuronide protects cartilage from progressive degeneration by blocking MMP-13

Collagenases (MMP-1, MMP-8, and MMP-13) play significant roles in the pathophysiology of osteoarthritis. Among these proteins, MMP-13 and MMP-8 are known for their catabolic roles in the degradation of the articular cartilage matrix. Using computational studies, we had previously observed that a metabolite of curcumin, Curcumin monoglucuronide (CMG), binds to MMPs involved in cartilage matrix destruction. The purpose of this study was to confirm the ability of CMG to protect cartilage by blocking the activity of these enzymes. The ability of CMG to bind and block the activities of MMP-13 and MMP-8 was established using several physicochemical methods. First, the protective effect of CMG on MMP-mediated cartilage destruction was demonstrated using cartilage explants in vitro. Second, the in vivo efficacy of CMG was tested by comparison with BI-4394, a specific MMP-13 inhibitor, using a rat anterior cruciate ligament transection (ACLT) model. These studies demonstrated that CMG was more effective than BI-4394 at preventing cartilage degeneration. In separate in vitro studies, CMG did not affect chondrocyte proliferation or the expression of NF-κB-mediated proinflammatory genes. Together, these findings demonstrate the therapeutic potential of CMG and emphasize the importance of inhibiting both MMP-13 and MMP-8 to achieve improved clinical outcomes.