Multipotent progenitors resident in the skeletal muscle interstitium exhibit robust BMP-dependent osteogenic activity and mediate heterotopic ossification.
Heterotopic ossification is a debilitating condition that can result from traumatic injury, surgery, or genetic disease. We investigated the cellular origins of heterotopic skeletogenesis in the mouse using lineage tracing and bioassays of heterotopic ossification based on intramuscular transplantation. We identified, characterized, and purified a tissue-resident stem/progenitor cell population that exhibits robust osteogenic potential and represents a major cell-of-origin for heterotopic ossification. These progenitors reside in the interstitium of skeletal muscle and other tissues, and are distinct from the endothelium, which does not exhibit osteogenic activity in response to bone morphogenetic protein 2 (BMP2) stimulation. Intramuscular transplantation, together with clonal analysis in culture, revealed that these progenitors are multipotent, exhibiting the capacity for both BMP-dependent skeletogenic differentiation and spontaneous adipogenic differentiation. Identifying the cells-of-origin responsible for heterotopic ossification provides a potential therapeutic target to treat, mitigate, or prevent this disabling condition.
Department of Molecular and Cell Biology, Center for Regenerative Biology, University of Connecticut Stem Cell Institute, University of Connecticut, Storrs, CT, USA.
Michael N
MN
Wosczyna
Arpita A
AA
Biswas
Catherine A
CA
Cogswell
David J
DJ
Goldhamer
D050156:Adipogenesis; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D002478:Cells, Cultured; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005838:Genotype; D051379:Mice; D016513:Mice, SCID; D039902:Multipotent Stem Cells; D018482:Muscle, Skeletal / Q000166:cytology*; D009999:Ossification, Heterotopic; D010012:Osteogenesis; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D042787:Receptor, TIE-2
C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D020794:Receptor Protein-Tyrosine Kinases; D042787:Receptor, TIE-2; C079086:Tek protein, mouse