title: Osteogenic potential of alpha smooth muscle actin expressing muscle resident progenitor cells.
abstract: Heterotopic ossification (HO) is a pathological process where bone forms in connective tissues such as skeletal muscle. Previous studies have suggested that muscle-resident non-myogenic mesenchymal progenitors are the likely source of osteoblasts and chondrocytes in HO. However, the previously identified markers of muscle-resident osteoprogenitors label up to half the osteoblasts within heterotopic lesions, suggesting other cell populations are involved. We have identified alpha smooth muscle actin (αSMA) as a marker of osteoprogenitor cells in bone and periodontium, and of osteo-chondro progenitors in the periosteum during fracture healing. We therefore utilized a lineage tracing approach to evaluate whether αSMACreERT2 identifies osteoprogenitors in the muscle. We show that in the muscle, αSMACreERT2 labels both perivascular cells, and satellite cells. αSMACre-labeled cells undergo osteogenic differentiation in vitro and form osteoblasts and chondrocytes in BMP2-induced HO in vivo. In contrast, Pax7CreERT2-labeled muscle satellite cells were restricted to myogenic differentiation in vitro, and rarely contributed to HO in vivo. Our data indicate that αSMACreERT2 labels a large proportion of osteoprogenitors in skeletal muscle, and therefore represents another marker of muscle-resident cells with osteogenic potential under HO-inducing stimulus. In contrast, muscle satellite cells make minimal contribution to bone formation in vivo.
authors.affiliation: Department of Reconstructive Sciences, University of Connecticut Health Center, Farmington, CT, USA.
authors.forename: Brya G
authors.initials: BG
authors.lastname: Matthews
authors.affiliation: Department of Reconstructive Sciences, University of Connecticut Health Center, Farmington, CT, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Torreggiani
authors.affiliation: Department of Reconstructive Sciences, University of Connecticut Health Center, Farmington, CT, USA.
authors.forename: Emilie
authors.initials: E
authors.lastname: Roeder
authors.affiliation: Department of Reconstructive Sciences, University of Connecticut Health Center, Farmington, CT, USA.
authors.forename: Igor
authors.initials: I
authors.lastname: Matic
authors.affiliation: Department of Physiology and Immunology, School of Medicine, University of Zagreb, Zagreb, Croatia.
authors.forename: Danka
authors.initials: D
authors.lastname: Grcevic
authors.affiliation: Department of Reconstructive Sciences, University of Connecticut Health Center, Farmington, CT, USA. Electronic address: ikalaj@uchc.edu.
authors.forename: Ivo
authors.initials: I
authors.lastname: Kalajzic
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D002462:Cell Membrane / Q000378:metabolism; D002469:Cell Separation; D005434:Flow Cytometry; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology*; D009999:Ossification, Heterotopic / Q000473:pathology; D010012:Osteogenesis; D051763:PAX7 Transcription Factor / Q000378:metabolism; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*
chemical_list: D000199:Actins; D015415:Biomarkers; D051763:PAX7 Transcription Factor; C497322:Pax7 protein, mouse; C544013:alpha-smooth muscle actin, mouse
keywords: Alpha smooth muscle actin; Heterotopic ossification; Mesenchymal progenitor; Osteogenesis; Satellite cell