Kaplan Frederick S, Glaser David L, Hebela Nader, Shore Eileen M
Departments of Orthopaedic Surgery and Medicine, The University of Pennsylvania School of Medicine, Silverstein 2, 3400 Spruce Street, Philadelphia, PA 19104-5283, USA.
J Am Acad Orthop Surg. 2004 Mar-Apr;12(2):116-25. doi: 10.5435/00124635-200403000-00007.
Heterotopic ossification, the formation of bone in soft tissue, requires inductive signaling pathways, inducible osteoprogenitor cells, and a heterotopic environment conducive to osteogenesis. Little is known about the molecular pathogenesis of this condition. Research into two rare heritable and developmental forms, fibrodysplasia ossificans progressiva and progressive osseous heteroplasia, has provided clinical, pathologic, and genetic insights. In fibrodysplasia ossificans progressiva, overexpression of bone morphogenetic protein 4 and underexpression of multiple antagonists of this protein highlight the potential role of a potent morphogenetic gradient. Research on fibrodysplasia ossificans progressiva also has led to the identification of the genetic cause of progressive osseous heteroplasia: inactivating mutations in the alpha subunit of the gene coding for the stimulatory G protein of adenylyl cyclase. Better understanding of the complex developmental and molecular pathology of these disorders may lead to more effective strategies to prevent and treat other, more common forms of heterotopic ossification.
异位骨化，即软组织中骨的形成，需要诱导信号通路、可诱导的骨祖细胞以及有利于骨生成的异位环境。对于这种病症的分子发病机制知之甚少。对两种罕见的遗传性和发育性形式，进行性骨化性纤维发育不良和进行性骨组织异位增生的研究，提供了临床、病理和遗传学方面的见解。在进行性骨化性纤维发育不良中，骨形态发生蛋白4的过表达以及该蛋白多种拮抗剂的低表达突出了一种强大形态发生梯度的潜在作用。对进行性骨化性纤维发育不良的研究还导致了对进行性骨组织异位增生遗传原因的识别：编码腺苷酸环化酶刺激性G蛋白的基因α亚基的失活突变。对这些疾病复杂的发育和分子病理学有更好的理解，可能会带来更有效的策略来预防和治疗其他更常见的异位骨化形式。
