Enzymatic Drivers of Cartilage Breakdown: Insights From a Bovine Osteoarthritis Explant Model.

Abstract

OBJECTIVE: Osteoarthritis (OA) is a progressive joint disease characterized by cartilage degradation driven by matrix-degrading enzymes. Reproducible ex vivo models are essential for studying early degenerative processes and evaluating potential therapeutics. However, there remains a lack of accessible, cost-effective models that accurately replicate the biochemical environment and early-stage damage of OA. This study aimed to develop and validate a bovine cartilage explant model that replicates key features of early OA through enzymatic induction of tissue damage. METHODS: Bovine stifle cartilage explants were exposed to combinations of matrix metalloproteinases, aggrecanases, and cartilage biomarkers. Tissue damage was evaluated histologically, and semiquantitative scoring was used to assess structural changes. Statistical analyses were conducted to determine differences between treatment groups. RESULTS: Enzyme-treated samples exhibited significantly greater cartilage degradation compared to controls. The addition of cartilage oligomeric matrix protein (COMP) increased tissue damage, suggesting an active role in matrix destabilization. In contrast, the inclusion of TIMP-3, a known protease inhibitor, did not reduce degradation, raising questions about its protective efficacy in this context. CONCLUSION: This chemically induced bovine model successfully simulates early cartilage degeneration consistent with OA pathology. Supported by recent literature on the roles of MMPs, ADAMTS-5, and COMP in joint disease, the model offers a valuable platform for future studies on OA mechanisms and therapeutic screening.