OPN plays a stage-specific role in atherosclerosis in LDLR-/- mice: OPN promotes calcification through the proinflammatory metabolite SVVYGLR at the early stage of diabetes and vascular disease, but OPN limits vascular cartilage-like metaplasia, endochondral mineralization and collagen accumulation at a later stage of disease progression to inhibit vascular calcification-induced damage. The gene discussed is SPP1; the disease is diabetes mellitus.