RIP1 perturbation induces chondrocyte necroptosis and promotes osteoarthritis pathogenesis

Receptor-interacting protein kinase 1 (RIP1)-mediated necroptosis plays a vital role in various diseases, but the involvement of RIP1 and its functional mechanism in osteoarthritis pathogenesis remains largely unknown. To identify molecular targets of RIP1 in chondrocytes, RNA sequencing was performed in chondrocytes treated with adenovirus expressing RIP1 or vector control. We found that 9857 genes were differentially expressed in chondrocytes after RIP1 overexpression. GO analysis indicated that DNA replication, chromosome segregation and regulation of cell cycle process were upregulated, while terms including cartilage development, skeletal system development, extracellular matrix organization, skeletal system morphogenesis, chondrocyte differentiation, collagen fibril organization and limb development were downregulated. Pathway analysis revealed that IL-17 signaling pathway, cell cycle, DNA replication, proteasome, TNF signaling pathway, cellular senescence and p53 signaling pathway were significantly upregulated by RIP1, meanwhile, ECM-receptor interaction, other glycan degradation and glycosaminoglycan degradation were downregulated. These results underscore the importance of RIP1 in OA by perturbing a series of essential events during disease progression such like cell cycle regulation, chondrocyte differentiation, inflammation and ECM remodeling.