To determine whether zinc finger protein 521 (Zfp521) has a chondroprotective effect by maintaining extracellular matrix (ECM) homeostasis to attenuate osteoarthritis (OA). In chondrocytes, Zfp521 was overexpressed or silenced to detect its effects on proliferation, apoptosis, and ECM homeostasis. Adenovirus encoding Zfp521 was injected into the knee joints of anterior cruciate ligament transection rats to test its efficacy against OA. Combined with proteomic analysis, the molecular mechanism of Zfp521 in cartilage degeneration was further explored....