Molecular and cellular mechanisms of heterotopic ossification.
Molecular and cellular mechanisms of heterotopic ossification.
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DOI：
10.14670/hh-29.1281
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发表时间：
2014-10
影响因子：
2
通讯作者：
Medici D
中科院分区：
文献类型：
--
作者：
Ramirez DM;Ramirez MR;Reginato AM;Medici D
异位骨化（HO）是一种使人衰弱的疾病，在这种疾病中，软骨和骨在肌肉、肌腱和韧带等软组织中形成，导致无法活动。这一过程是由创伤性损伤相关的炎症所诱发。在一种极其罕见的名为进行性骨化性纤维发育不良（FOP）的遗传性疾病中，与轻微软组织损伤相关的炎症以及遗传性基因突变共同导致大量异位骨化，在患者一生中逐渐恶化，导致异位骨骼的形成。已表明骨形态发生蛋白I型受体ALK2的激活突变会导致FOP患者的异位病变，但近期研究表明，刺激异位骨化还需要其他事件，包括感觉神经元的激活、肥大细胞脱颗粒、淋巴细胞浸润、骨骼肌细胞死亡以及内皮 - 间充质转化（EndMT）。在这篇综述中，我们讨论了近期的证据和机制数据，这些数据描述了导致异位骨形成的细胞和分子机制。
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.