Department of Cranio-Maxillofacial Surgery, University of Münster, Albert-Schweitzer-Campus 1, 48149 Münster, Germany.
Cells. 2019 Feb 3;8(2):121. doi: 10.3390/cells8020121.
Bone formation and regeneration is a multistep complex process crucially determined by the formation of blood vessels in the growth plate region. This is preceded by the expression of growth factors, notably the vascular endothelial growth factor (VEGF), secreted by osteogenic cells, as well as the corresponding response of endothelial cells, although the exact mechanisms remain to be clarified. Thereby, coordinated coupling between osteogenesis and angiogenesis is initiated and sustained. The precise interplay of these two fundamental processes is crucial during times of rapid bone growth or fracture repair in adults. Deviations in this balance might lead to pathologic conditions such as osteoarthritis and ectopic bone formation. Besides VEGF, the recently discovered important regulatory and modifying functions of microRNAs also support this key mechanism. These comprise two principal categories of microRNAs that were identified with specific functions in bone formation (osteomiRs) and/or angiogenesis (angiomiRs). However, as hypoxia is a major driving force behind bone angiogenesis, a third group involved in this process is represented by hypoxia-inducible microRNAs (hypoxamiRs). This review was focused on the identification of microRNAs that were found to have an active role in osteogenesis as well as angiogenesis to date that were termed "CouplingmiRs (CPLGmiRs)". Outlined representatives therefore represent microRNAs that already have been associated with an active role in osteogenic-angiogenic coupling or are presumed to have its potential. Elucidation of the molecular mechanisms governing bone angiogenesis are of great relevance for improving therapeutic options in bone regeneration, tissue-engineering, and the treatment of bone-related diseases.
骨形成和再生是一个多步骤的复杂过程，关键取决于生长板区域血管的形成。这之前是生长因子的表达，特别是血管内皮生长因子（VEGF），由成骨细胞分泌，以及内皮细胞的相应反应，尽管确切的机制仍有待阐明。由此，骨生成和血管生成之间的协调偶联被启动并维持。在成人快速骨生长或骨折修复期间，这两个基本过程的精确相互作用至关重要。这种平衡的偏差可能导致病理状况，如骨关节炎和异位骨形成。除了 VEGF 之外，最近发现的 microRNAs 的重要调节和修饰功能也支持这一关键机制。这些包括两类主要的 microRNAs，它们在骨形成（osteomiRs）和/或血管生成（angiomiRs）中具有特定的功能。然而，由于缺氧是骨血管生成的主要驱动力，因此涉及这一过程的第三组是缺氧诱导的 microRNAs（hypoxamiRs）。这篇综述集中于鉴定迄今为止发现的在骨生成和血管生成中具有积极作用的 microRNAs，这些 microRNAs被称为“CouplingmiRs（CPLGmiRs）”。因此，列出的代表是已经与成骨-血管生成偶联的积极作用相关联的 microRNAs，或者被认为具有其潜力的 microRNAs。阐明控制骨血管生成的分子机制对于改善骨再生、组织工程和骨相关疾病治疗中的治疗选择具有重要意义。
