Hypoxia-inducible factors (HIFs) are core regulators of the hypoxia response. HIF signaling is activated in the local physiological and pathological hypoxic environment, acting on downstream target genes to synthesize the corresponding proteins and regulate the hypoxic stress response. HIFs belong to the hypoxia-activated transcription family and contain two heterodimeric transcription factors, HIF-α and HIF-β. Under hypoxia, the dimer formed by HIF-α binding to HIF-β translocates into the nucleus and binds to the hypoxia response element (HRE) to induce transcription of a series of genes. HIF-1α plays an important role in innate bone development and acquired bone regeneration. HIF-1α promotes bone regeneration mainly through the following two pathways: (1) By regulating angiogenesis-osteoblast coupling to promote bone regeneration; and (2) by inducing metabolic reprogramming in osteoblasts, promoting cellular anaerobic glycolysis, ensuring the energy supply of osteoblasts under hypoxic conditions, and further promoting bone regeneration and repair. This article reviews recent basic research on HIF-1α and its role in promoting osteogenesis, discusses the possible molecular mechanisms, introduces the hypoxia-independent role of HIF-1α and reviews the application prospects of HIF-1α in tissue engineering.
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