景鹏举, 陈海伟, 王志强, 成鹏. 异位骨化的分子机制与靶向治疗研究进展. 2025. biomedRxiv.202506.00002
异位骨化的分子机制与靶向治疗研究进展
通讯作者: 成鹏, 1415047901@qq.com
DOI:10.12201/bmr.202506.00002
Corresponding author: chengpeng, 1415047901@qq.com
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摘要:异位骨化(Heterotopic Ossification, HO)是一种在软组织中形成病理性骨组织的现象,其病理特征为成熟的板层骨结构。HO常见于关节置换术后、脊髓损伤、爆炸伤及遗传性疾病(如纤维发育不良性进行性骨化症FOP)等,临床表现为疼痛、关节功能障碍及生活质量下降。其发病机制涉及成骨前体细胞的异常分化、BMP/SMAD信号通路的激活、炎症微环境失衡及多种信号通路(如Hedgehog、Wnt/β-catenin、mTOR)的相互作用。目前,非甾体抗炎药(NSAIDs)和放疗是主要的预防手段,手术切除为唯一有效治疗方法,但存在复发风险。新兴的靶向治疗(如BMP抑制剂LDN-193189、Hedgehog抑制剂Gant58等)和基因治疗展现出潜力,但仍需进一步临床验证。本文系统综述了HO的病因、分子机制及治疗进展,为未来研究提供方向。
Abstract: Heterotopic Ossification (HO) is a phenomenon of pathological bone tissue formation in soft tissues, and its pathological feature is a mature lamellar bone structure. HO is commonly seen after joint replacement surgery, spinal cord injury, blast injury and genetic diseases (such as fibrodysplasia progressive ossification FOP), etc. The clinical manifestations are pain, joint dysfunction and decreased quality of life. Its pathogenesis involves the abnormal differentiation of osteogenic precursor cells, the activation of the BMP/SMAD signaling pathway, the imbalance of the inflammatory microenvironment, and the interaction of multiple signaling pathways (such as Hedgehog, Wnt/β-catenin, mTOR). At present, non-steroidal anti-inflammatory drugs (NSAIDs) and radiotherapy are the main preventive measures. Surgical resection is the only effective treatment method, but there is a risk of recurrence. Emerging targeted therapies (such as BMP inhibitor DLN-193189 and Hedgehog inhibitor Gant58) and gene therapy have shown potential, but further clinical verification is still needed. This article systematically reviews the etiology, molecular mechanism and therapeutic progress of HO, providing a direction for future research.
Key words: Heterotopic; Ossification, Ectopic; ossification, BMP/SMAD; signaling pathway, Inflammatory; microenvironment, Targeted; therapy提交时间:2025-06-03
版权声明:作者本人独立拥有该论文的版权,预印本系统仅拥有论文的永久保存权利。任何人未经允许不得重复使用。 -
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