Jiangxi Province Key Laboratory of Tumor Pathogens and Molecular Pathology, Department of Pathophysiology, School of Basic Medicine Sciences, Nanchang University Medical College, Nanchang, Jiangxi 330006, P.R. China.
Mol Med Rep. 2019 Oct;20(4):2979-2989. doi: 10.3892/mmr.2019.10556. Epub 2019 Aug 6.
Heterotopic ossification (HO) refers to the appearance of osteoblasts in soft tissues under pathological conditions, such as trauma or infection. HO arises in an unpredictable way without any recognizable initiation. Activin receptor‑like kinase‑2 (ALK2) is a type I cell surface receptor for bone morphogenetic proteins (BMPs). The dysregulation of ALK2 signaling is associated with a variety of diseases, including cancer and HO. At present, the prevention and treatment of HO in the clinic predominantly includes nonsteroidal anti‑inflammatory drugs (NSAIDs), bisphosphonates and other drug treatments, low‑dose local radiation therapy and surgical resection, rehabilitation treatment and physical therapy. However, most of these therapies have adverse effects. These methods do not prevent the occurrence of HO. The pathogenesis of HO is not being specifically targeted; the current treatment strategies target the symptoms, not the disease. These treatments also cannot solve the fundamental problem of the occurrence of HO. Therefore, scholars have been working to develop targeted therapies based on the pathogenesis of HO. The present review focuses on advances in the understanding of the underlying mechanisms of HO, and possible options for the prevention and treatment of HO. In addition, the role of ALK2 in the process of HO is introduced and the progress made towards the targeted inhibition of ALK2 is discussed. The present study aims to offer a platform for further research on possible targets for the prevention and treatment of HO.
异位骨化(HO)是指在创伤或感染等病理条件下,成骨细胞出现在软组织中。HO 的发生方式不可预测,没有任何可识别的起始点。激活素受体样激酶-2(ALK2)是骨形成蛋白(BMPs)的一种 I 型细胞表面受体。ALK2 信号通路的失调与多种疾病有关,包括癌症和 HO。目前,临床上 HO 的预防和治疗主要包括非甾体抗炎药(NSAIDs)、双膦酸盐等药物治疗、低剂量局部放射治疗和手术切除、康复治疗和物理治疗。然而,这些疗法大多有不良反应。这些方法不能预防 HO 的发生。HO 的发病机制没有被专门针对;目前的治疗策略针对的是症状,而不是疾病。这些治疗方法也不能解决 HO 发生的根本问题。因此,学者们一直在努力开发基于 HO 发病机制的靶向治疗方法。本综述重点介绍了对 HO 发病机制的理解的进展,以及预防和治疗 HO 的可能选择。此外,还介绍了 ALK2 在 HO 过程中的作用以及靶向抑制 ALK2 所取得的进展。本研究旨在为 HO 的预防和治疗的可能靶点的进一步研究提供一个平台。