ECM remodeling features in reparative chondrocytes during knee osteoarthritis

Background: Knee osteoarthritis (KOA) is characterized by progressive cartilage degeneration and disruption of extracellular matrix (ECM) homeostasis. Chondrocytes are not a homogeneous or static population during disease progression but exhibit pronounced functional heterogeneity. Although single-cell transcriptomic studies have identified multiple chondrocyte states in osteoarthritic cartilage, how these states dynamically relate to ECM remodeling and disease progression remains incompletely understood. Methods: cultured human articular chondrocytes. Results: induced expression of multiple RepC-associated genes and enhanced SMAD2/3 phosphorylation, recapitulating key features of the RepC state observed in single-cell analyses. Conclusion: These findings highlight ECM remodeling features of reparative chondrocytes during KOA and support a state-centric view in which disproportionate representation of reparative states within the pseudotime trajectory framework is associated with maladaptive ECM remodeling in KOA.