Division of Endocrinology and Metabolism, Department of Medicine, the Institute for Human Genetics, the Program in Craniofacial Biology, University of California, San Francisco, CA 94143, USA.
Biomolecules. 2024 Mar 16;14(3):357. doi: 10.3390/biom14030357.
Inflammation is a major driver of heterotopic ossification (HO), a condition of abnormal bone growth in a site that is not normally mineralized.
This review will examine recent findings on the roles of inflammation and the immune system in fibrodysplasia ossificans progressiva (FOP). FOP is a genetic condition of aggressive and progressive HO formation. We also examine how inflammation may be a valuable target for the treatment of HO. Rationale/Recent findings: Multiple lines of evidence indicate a key role for the immune system in driving FOP pathogenesis. Critical cell types include macrophages, mast cells, and adaptive immune cells, working through hypoxia signaling pathways, stem cell differentiation signaling pathways, vascular regulatory pathways, and inflammatory cytokines. In addition, recent clinical reports suggest a potential role for immune modulators in the management of FOP.
The central role of inflammatory mediators in HO suggests that the immune system may be a common target for blocking HO in both FOP and non-genetic forms of HO. Future research focusing on the identification of novel inflammatory targets will help support the testing of potential therapies for FOP and other related conditions.
炎症是异位骨化（HO）的主要驱动因素，HO 是一种异常骨生长在通常不会矿化的部位的情况。
本综述将探讨炎症和免疫系统在纤维性骨发育不良进展性（FOP）中的作用的最新发现。FOP 是一种具有侵袭性和进行性 HO 形成的遗传性疾病。我们还研究了炎症如何可能成为 HO 治疗的有价值的靶点。
理由/最新发现：多项证据表明免疫系统在驱动 FOP 发病机制中起着关键作用。关键细胞类型包括巨噬细胞、肥大细胞和适应性免疫细胞，通过缺氧信号通路、干细胞分化信号通路、血管调节通路和炎症细胞因子发挥作用。此外，最近的临床报告表明免疫调节剂在 FOP 的治疗中可能具有潜在作用。
炎症介质在 HO 中的核心作用表明，免疫系统可能是阻止 FOP 和非遗传性 HO 中 HO 的共同靶点。未来专注于识别新的炎症靶点的研究将有助于支持 FOP 和其他相关疾病潜在治疗方法的测试。
