Uhrf1 determines osteophyte fate by regulating differentiation of synovial mesenchymal progenitor cells

This study investigates the role of Uhrf1 in osteophyte formation, building on previous findings of the role of Uhrf1 in cartilage proliferation and chondrogenic differentiation. We used mesenchymal stem cell-specific Uhrf1 knockout (cKO) mice to evaluate osteophyte development and cartilage degeneration at 2 and 12 weeks post-DMM surgery. At 2 weeks, cKO mice had significantly smaller osteophytes with reduced width, area, and maturity scores compared to controls. At 12 weeks, despite similar maturity scores, osteophytes in cKO mice were still smaller, and cartilage degeneration was more severe. Uhrf1 knockdown in human synovial cells led to decreased proliferation and chondrogenic differentiation. These results suggest that Uhrf1 is essential for early osteophyte formation and chondrogenesis, with its effects continuing as osteophytes mature. Additionally, osteophytes seem to protect against cartilage degeneration in OA, and RNA-seq analysis revealed that Uhrf1 deficiency upregulates genes that negatively affect cell devel