Abstract: 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.
Dr. Kaplan is Isaac and Rose Nassau Professor of Orthopaedic Molecular Medicine, Departments of Orthopaedic Surgery and Medicine, The University of Pennsylvania School of Medicine, Philadelphia, PA. Dr. Glaser is The Cali Family Assistant Professor of Orthopaedic Molecular Medicine, Department of Orthopaedic Surgery, The University of Pennsylvania School of Medicine. Dr. Hebela is Research Fellow, Department of Orthopaedic Surgery, The University of Pennsylvania School of Medicine. Dr. Shore is Research Associate Professor of Orthopaedics and Genetics, Departments of Orthopaedic Surgery and Genetics, The University of Pennsylvania School of Medicine.
None of the following authors or the departments with which they are affiliated has received anything of value from or owns stock in a commercial company or institution related directly or indirectly to the subject of this article: Dr. Kaplan, Dr. Glaser, and Dr. Hebela. Dr. Shore or the departments with which she is affiliated have received research or institutional support from Johnson & Johnson.
Reprint requests: Dr. Kaplan, The University of Pennsylvania Medical Center, Silverstein 2, 3400 Spruce Street, Philadelphia, PA 19104‐5283.