| Osteoporosis and the associated difficulty in fracture repair pose an increasingly severe global public health challenge, fundamentally linked to insufficient bone formation mediated by osteoblasts. In recent years, metabolic reprogramming has been found to play a core role in cell fate determination. This review systematically summarizes the latest research progress on osteoblast metabolic reprogramming, elaborates on the spatiotemporal dynamic changes of various metabolic pathways during differentiation, further explores the specific mechanisms by which metabolic reprogramming directly drives bone formation through providing metabolic intermediates as epigenetic regulatory cofactors, regulating reactive oxygen species balance, and supporting collagen synthesis, and summarizes the precise regulation of metabolic reprogramming by key signaling pathways such as Wnt/β-catenin, HIF-1α, PI3K/AKT/mTORC1, and YAP/TAZ. Finally, this article looks forward to new strategies for bone regeneration, including small molecule drugs, gene therapy, and functional biomaterials targeting osteoblast metabolism, aiming to provide new theoretical basis and innovative ideas for the prevention and treatment of metabolic bone diseases. |