title: Stromal cells of fibrodysplasia ossificans progressiva lesions express smooth muscle lineage markers and the osteogenic transcription factor Runx2/Cbfa-1: clues to a vascular origin of heterotopic ossification?
abstract: Fibrodysplasia ossificans progressiva (FOP) is a rare heritable genetic disorder, which is characterized pathologically by sporadic episodes of explosive growth of mesenchymal cells in skeletal muscle followed by cellular differentiation to heterotopic bone through an endochondral process. This study examined the histological origin and differentiation state of stromal cells in early FOP lesions and investigated the association between the phenotype of these FOP cells and bone formation. Interestingly, FOP lesional stromal cells were found to display characteristics of the smooth muscle (SM) cell lineage and are therefore potentially of vascular origin. These cells co-express multiple SM lineage markers along with multiple proteins associated with bone formation including the obligate osteogenic transcription factor Runx2/Cbfa-1. It is hypothesized that the stromal cells of early FOP lesions may be locally recruited vascular cells or cells of the bone marrow stroma and that these cells maintain the potential (given the correct environmental stimuli) to differentiate along an endochondral ossification pathway.
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, University of Cambridge, Cambridge, UK.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Hegyi
authors.forename: Francis H
authors.initials: FH
authors.lastname: Gannon
authors.forename: David L
authors.initials: DL
authors.lastname: Glaser
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Shore
authors.forename: Frederick S
authors.initials: FS
authors.lastname: Kaplan
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Shanahan
mesh_terms: D001706:Biopsy; D002454:Cell Differentiation; D050659:Core Binding Factor Alpha 1 Subunit; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D058574:Integrin-Binding Sialoprotein; D018613:Microscopy, Confocal; D009130:Muscle, Smooth / Q000098:blood supply / Q000378:metabolism*; D009221:Myositis Ossificans / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins; D015675:Osteocalcin / Q000378:metabolism; D012795:Sialoglycoproteins / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; C546871:IBSP protein, human; D058574:Integrin-Binding Sialoprotein; D009363:Neoplasm Proteins; D012795:Sialoglycoproteins; D014157:Transcription Factors; D015675:Osteocalcin