State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
FASEB J. 2022 Oct;36(10):e22520. doi: 10.1096/fj.202200329RR.
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.
缺氧诱导因子 (HIFs) 是缺氧反应的核心调节剂。HIF 信号在局部生理和病理缺氧环境中被激活，作用于下游靶基因合成相应的蛋白质，调节缺氧应激反应。HIFs 属于缺氧激活转录家族，包含两个异二聚体转录因子，HIF-α和 HIF-β。在缺氧条件下，HIF-α与 HIF-β结合形成的二聚体易位到细胞核内，并与缺氧反应元件 (HRE) 结合，诱导一系列基因的转录。HIF-1α 在先天骨发育和获得性骨再生中发挥着重要作用。HIF-1α 主要通过以下两种途径促进骨再生：(1) 通过调节血管生成-成骨偶联促进骨再生；(2) 通过诱导成骨细胞代谢重编程，促进细胞无氧糖酵解，保证成骨细胞在缺氧条件下的能量供应，进而促进骨再生和修复。本文综述了 HIF-1α 及其在促进成骨作用方面的基础研究新进展，探讨了可能的分子机制，介绍了 HIF-1α 的缺氧非依赖性作用，并对 HIF-1α 在组织工程中的应用前景进行了综述。
