First Clinical Medical School, Nanchang University, Nanchang, 330006, Jiangxi Province, China.
Department of Pathophysiology, School of Basic Medical Sciences, Nanchang University, 461 BaYi Avenue, Nanchang, 330006, Jiangxi Province, China.
Cell Commun Signal. 2020 Feb 7;18(1):20. doi: 10.1186/s12964-020-0509-1.
Heterotopic ossification (HO) refers to the formation of bone tissue outside the normal skeletal system. According to its pathogenesis, HO is divided into hereditary HO and acquired HO. There currently lack effective approaches for HO prevention or treatment. A deep understanding of its pathogenesis will provide promising strategies to prevent and treat HO. Studies have shown that the hypoxia-adaptive microenvironment generated after trauma is a potent stimulus of HO. The hypoxic microenvironment enhances the stability of hypoxia-inducible factor-1α (HIF-1α), which regulates a complex network including bone morphogenetic proteins (BMPs), vascular endothelial growth factor (VEGF), and neuropilin-1 (NRP-1), which are implicated in the formation of ectopic bone. In this review, we summarize the current understanding of the triggering role and underlying molecular mechanisms of the hypoxic microenvironment in the initiation and progression of HO, focusing mainly on HIF-1 and it's influenced genes BMP, VEGF, and NRP-1. A better understanding of the role of hypoxia in HO unveils novel therapeutic targets for HO that reduce the local hypoxic microenvironment and inhibit HIF-1α activity. Video Abstract. (MP4 52403 kb).
异位骨化（HO）是指在正常骨骼系统以外形成骨组织。根据其发病机制，HO 分为遗传性 HO 和获得性 HO。目前缺乏预防或治疗 HO 的有效方法。深入了解其发病机制将为预防和治疗 HO 提供有希望的策略。研究表明，创伤后产生的缺氧适应微环境是 HO 的有力刺激因素。缺氧微环境增强了缺氧诱导因子-1α（HIF-1α）的稳定性，后者调节了一个包括骨形态发生蛋白（BMPs）、血管内皮生长因子（VEGF）和神经纤毛蛋白-1（NRP-1）在内的复杂网络，这些蛋白参与异位骨的形成。在这篇综述中，我们总结了缺氧微环境在 HO 的发生和进展中触发作用及其潜在分子机制的最新认识，主要集中在 HIF-1 及其受影响的基因 BMP、VEGF 和 NRP-1 上。更好地了解缺氧在 HO 中的作用揭示了减少局部缺氧微环境和抑制 HIF-1α活性的 HO 的新治疗靶点。视频摘要。（MP4 52403 kb）。
