Multi‑omics integration in osteoarthritis: Unraveling cell‑type‑specific gene‑metabolite networks for precision...

Osteoarthritis (OA) is a heterogeneous joint disorder lacking disease‑modifying therapies. Recent advances in single‑cell transcriptomics, metabolomics, lipidomics, and spatial omics have enabled the reconstruction of cell‑type‑specific gene‑metabolite networks and revealed that metabolic reprogramming differs markedly across chondrocyte subsets, synovial fibroblasts and immune cells. Lipid metabolism disturbances, particularly those involving glycerophospholipids, sphingolipids and cholesterol, are consistently linked to OA severity and pain generation. Integrative multi‑omics approaches further facilitate molecular endotyping, informing patient stratification and endotype‑driven clinical trial design. However, a systematic synthesis of these emerging findings is still lacking. This review critically synthesizes current multi‑omics integration strategies, delineates cell‑type‑specific metabolic networks derived from transcriptomic and metabolomic data and discusses their implications for precision medicine in OA, while also considering the emerging contributions of spatial omics technologies.