Osteoarthritis year in review 2025: Biology.

OBJECTIVE

To synthesize recent advances in developmental biology, mechanobiology, metabolism, and tissue engineering as they relate to cartilage biology and osteoarthritis (OA).

DESIGN

Narrative review integrating peer-reviewed studies covering chondrocyte ontogeny, mechanical and metabolic regulation, disease pathogenesis, and regenerative strategies.

RESULTS

SOX9+ progenitors persist postnatally and contribute to cartilage and bone repair. Mechanotransductive signaling through TRPV4 and PIEZO1 ion channels, together with cytoskeletal regulators, orchestrate cartilage matrix remodeling and inflammation. Metabolic rewiring driven by TGF-β, HIF1α, and fatty acid oxidation programs is critical for joint development and OA pathology. Sex-linked lipidomic signatures and enhancer reprogramming shape disease risk and response. Engineered tissues using nasal chondrocytes and transcriptional enhancers offer repair potential.

CONCLUSIONS

OA arises from disruption of conserved developmental, metabolic, and mechanical programs. Targeted interventions restoring transcriptional fidelity, metabolic balance, and tissue mechanics offer translational promise.