The role of endothelial-mesenchymal transition in heterotopic ossification

Authors

  • Damian Medici,

    Corresponding author
    1. Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
    2. Department of Developmental Biology, Harvard School of Dental Medicine, Harvard Medical School, Boston, MA, USA
    • Harvard Medical School, 190 Longwood Avenue, REB 406, Boston, MA 02115, USA.
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  • Bjorn R Olsen

    1. Department of Developmental Biology, Harvard School of Dental Medicine, Harvard Medical School, Boston, MA, USA
    2. Department of Cell Biology, Harvard Medical School, Boston, MA, USA
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Abstract

Heterotopic ossification (HO) is a process by which bone forms in soft tissues, in response to injury, inflammation, or genetic disease. This usually occurs by initial cartilage formation, followed by endochondral ossification. A rare disease called fibrodysplasia ossificans progressiva (FOP) allows this mechanism to be induced by a combination of genetic mutation and acute inflammatory responses. FOP patients experience progressive HO throughout their lifetime and form an ectopic skeleton. Recent studies on FOP have suggested that heterotopic cartilage and bone is of endothelial origin. Vascular endothelial cells differentiate into skeletal cells through a mesenchymal stem cell intermediate that is generated by endothelial-mesenchymal transition (EndMT). Local inflammatory signals and/or other changes in the tissue microenvironment mediate the differentiation of endothelial-derived mesenchymal stem cells into chondrocytes and osteoblasts to induce HO. We discuss the current evidence for the endothelial contribution to heterotopic bone formation. © 2012 American Society for Bone and Mineral Research.

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