Schematic of degenerative disease progression in OA and possible CSPC-based therapies. a | Potential therapeutic strategies involving CSPCs in early OA could enhance the capacity of these cells for joint resurfacing, ECM production and chondroprotection. b | ECM loss and structural changes in late-stage OA cartilage enable cell passage, but several challenges and questions regarding the role of migratory CSPCs remain to be addressed. Abbreviations: BMP, bone morphogenic protein; CSPC, cartilage stem/progenitor cell; ECM, extracellular matrix; IL-Ra, IL-1 receptor antagonist; OA, osteoarthritis; TGF-β, transforming growth factor β; TIMP, tissue inhibitor of metalloproteinases.