Identifying Progenitor Cells of Heterotopic Ossification

Heterotopic Ossification (HO) is the abnormal formation of bone within extraskeletal soft tissues. The condition can occur through both genetic and acquired means. Acquired cases of HO result from invasive surgery or traumatic injuries, with increasing prevalence of ectopic skeletogenesis as a result of combat-related blast injuries. HO has been characterized to some extent, including the histological features and the mutation underlying the genetic form, but the cells resident in skeletal muscle that represent the progenitors of heterotopic bone have yet to be determined. Only a few publications have attempted to definitively determine the progenitor cells in this disorder. Findings have been inconclusive, but cell types such as skeletal muscle satellite cells, pericytes and endothelial cells, mesenchymal progenitors, and circulating hematopoietic cells were considered attractive candidates due to accessibility and displays of osteogenic characteristics. The aim of this study was to determine the progenitor cells of HO. To accomplish this goal, lineage tracing and bioassays of heterotopic ossification were used to identify and characterize the progenitor cell type. We identified a population of Tie2+ cells that are non-endothelial (CD31-) in origin and represent a major source of progenitors for HO. The identification of the progenitor is crucial to establishing any future therapeutic agents or treatments for HO