Damian Medici

Signals from the microenvironment trigger epithelial-mesenchymal transition in development and disease through multiple, crosstalking pathways.

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.

Endothelial plasticity, the ability of endothelial cells to alter their lineage commitment to generate other cell types, is involved in many developmental and pathological processes. It was recently shown that vascular endothelial cells are converted to a mesenchymal stem cell phenotype through a process known as endothelial-mesenchymal transition (EndMT). EndMT is characterized as a morphological and phenotypical transformation of endothelial cells that has been implicated in cardiac development, cancer, fibrosis and heterotopic ossification. Here we describe the molecular and cellular basis for EndMT-dependent generation of endothelial-derived stem cells and their potential for tissue engineering and regenerative medicine.