Ramirez Diana M, Ramirez Melissa R, Reginato Anthony M, Medici Damian
Department of Orthopaedics, Warren Alpert Medical School of Brown University, and Cardiovascular Research Center, Rhode Island Hospital, Providence, RI, USA.
Department of Orthopaedics, and Division of Rheumatology, Department of Medicine, Warren Alpert Medical School of Brown University, Providence, RI, USA.
Histol Histopathol. 2014 Oct;29(10):1281-5. doi: 10.14670/HH-29.1281. Epub 2014 May 5.
Heterotopic ossification (HO) is a debilitating condition in which cartilage and bone forms in soft tissues such as muscle, tendon, and ligament causing immobility. This process is induced by inflammation associated with traumatic injury. In an extremely rare genetic disorder called fibrodysplasia ossificans progessiva (FOP), a combination of inflammation associated with minor soft tissue injuries and a hereditary genetic mutation causes massive HO that progressively worsens throughout the patients' lifetime leading to the formation of an ectopic skeleton. An activating mutation in the BMP type I receptor ALK2 has been shown to contribute to the heterotopic lesions in FOP patients, yet recent studies have shown that other events are required to stimulate HO including activation of sensory neurons, mast cell degranulation, lymphocyte infiltration, skeletal myocyte cell death, and endothelial-mesenchymal transition (EndMT). In this review, we discuss the recent evidence and mechanistic data that describe the cellular and molecular mechanisms that give rise to heterotopic bone.
异位骨化（HO）是一种使人衰弱的病症，其中软骨和骨在诸如肌肉、肌腱和韧带等软组织中形成，导致活动障碍。这个过程由与创伤性损伤相关的炎症引发。在一种极其罕见的遗传性疾病——进行性骨化性纤维发育不良（FOP）中，与轻微软组织损伤相关的炎症和遗传性基因突变共同导致大量异位骨化，在患者的一生中逐渐恶化，导致异位骨骼的形成。已证明骨形态发生蛋白（BMP）I型受体ALK2中的激活突变会导致FOP患者出现异位病变，但最近的研究表明，还需要其他事件来刺激异位骨化，包括感觉神经元的激活、肥大细胞脱颗粒、淋巴细胞浸润、骨骼肌细胞死亡和内皮-间充质转化（EndMT）。在这篇综述中，我们讨论了描述导致异位骨形成的细胞和分子机制的最新证据和机制数据。
