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).

中文翻译：

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低氧微环境：异位骨化进展的驱动力。

异位骨化（HO）是指正常骨骼系统外部骨组织的形成。根据其发病机理，HO分为遗传性HO和获得性HO。当前缺乏预防或治疗HO的有效方法。对它的发病机理的深入了解将为预防和治疗HO提供有希望的策略。研究表明，创伤后产生的低氧适应性微环境是HO的有效刺激。低氧微环境增强了缺氧诱导因子-1α（HIF-1α）的稳定性，该因子调节包括骨形态发生蛋白（BMP），血管内皮生长因子（VEGF）和神经纤维蛋白-1（NRP-1）在内的复杂网络，这与异位骨的形成有关。在这篇评论中 我们总结了目前对低氧微环境在HO的起始和进展中的触发作用和潜在分子机制的理解，主要集中在HIF-1及其受其影响的基因BMP，VEGF和NRP-1。对缺氧在HO中的作用的更好理解揭示了HO的新治疗靶标，这些靶标可减少局部缺氧的微环境并抑制HIF-1α活性。录像摘要。（MP4 52403 kb）。