The latest research progress on cell death in the pathogenesis of knee osteoarthritis

FAN Qi; DONG Zhong; MA Chenxi

doi:10.13431/j.cnki.immunol.j.20250073

Abstract：Knee osteoarthritis(KOA)is a chronic joint disease characterized by degeneration of articular cartilage and joint pain.Its pathogenesis is complex,involving cell death,inflammatory responses and the interaction of various signaling pathways.Apoptosis is activated by Caspase family proteins and DNA endonucleases,leading to cellular dysfunction and promoting the degeneration of articular cartilage.Pyroptosis is a form of programmed cell death triggered by inflammasome activation,involving the activation of nucleotide-binding oligomeric domain-like receptor protein 3 inflammasome,which leads to the release of pro-inflammatory cytokines such as interleukin(IL)-6,IL-1 β and tumor necrosis factor-α.This release intensifies local inf/lammation and accelerates the progression of the disease.Ferroptosis is driven by iron-catalyzed lipid peroxidation,which induces the rupture of chondrocyte cell membranes and the degradation of matrix,thereby promoting joint degeneration.In addition,autophagy plays a dual role in KOA:moderate autophagy supports chondrocyte repair,while excessive autophagy may promote joint destruction,cartilage matrix degradation and subchondral bone sclerosis.The PI3K/AKT,NF-κB,Wnt/β-catenin and Hedgehog signaling pathways can regulate the growth,differentiation,proliferation,migration and apoptosis of articular chondrocytes.Single-cell RNA sequencing technology has provided new insights into the cellular heterogeneity and molecular mechanisms in the pathogenesis of KOA.This review explores the mechanisms of cell death in KOA,with a focus on the roles of pro-inflammatory cytokines,signaling pathway,and single-cell RNA sequencing techniques in the occurrence and progression of KOA.