Molecular and cellular mechanisms of heterotopic ossification
Diana M. Ramirez1-4, Melissa R. Ramirez1-5, Anthony M. Reginato5 and Damian Medici1-4
1Department of Orthopaedics, Warren Alpert Medical School of Brown University, Providence, RI, USA, 2Division of Hematology/Oncology, Department of Medicine, Warren Alpert Medical School of Brown University, Providence, RI, USA, 3Center for Regenerative Medicine, Rhode Island Hospital, Providence, RI, USA, 4Cardiovascular Research Center, Rhode Island Hospital, Providence, RI, USA and 5Division of Rheumatology, Department of Medicine, Warren Alpert Medical School of Brown University, Providence, RI, USA
Offprint requests to: Damian Medici, Ph.D., Assistant Professor of Orthopaedics and Medicine, Warren Alpert Medical School of Brown University, Director, Center for Regenerative Medicine, Rhode Island Hospital, 1 Hoppin Street, Coro West, Suite 402C, Providence, RI 02903, USA. e-mail: damian_medici@brown.edu
Summary. Heterotopic ossification (HO) is a debilitating condition in which cartilage and bone forms in soft tissues such as muscle, tendon, and ligament causing immobility. This process is induced by inflammation associated with traumatic injury. In an extremely rare genetic disorder called fibrodysplasia ossificans progessiva (FOP), a combination of inflammation associated with minor soft tissue injuries and a hereditary genetic mutation causes massive HO that progressively worsens throughout the patients' lifetime leading to the formation of an ectopic skeleton. An activating mutation in the BMP type I receptor ALK2 has been shown to contribute to the heterotopic lesions in FOP patients, yet recent studies have shown that other events are required to stimulate HO including activation of sensory neurons, mast cell degranulation, lymphocyte infiltration, skeletal myocyte cell death, and endothelial-mesenchymal transition (EndMT). In this review, we discuss the recent evidence and mechanistic data that describe the cellular and molecular mechanisms that give rise to heterotopic bone. Histol Histopathol 29, 1281-1285 (2014)
Key words: Heterotopic ossification, HO, Fibro-dysplasia ossificans progressiva, FOP, Bone
DOI: 10.14670/HH-29.1281