Dysregulation of local stem/progenitor cells as a common cellular mechanism for heterotopic ossification.
Heterotopic ossification (HO), the abnormal formation of true marrow-containing bone within extraskeletal soft tissues, is a serious bony disorder that may be either acquired or hereditary. We utilized an animal model of the genetic disorder fibrodysplasia ossificans progressiva to examine the cellular mechanisms underlying HO. We found that HO in these animals was triggered by soft tissue injuries and that the effects were mediated by macrophages. Spreading of HO beyond the initial injury site was mediated by an abnormal adaptive immune system. These observations suggest that dysregulation of local stem/progenitor cells could be a common cellular mechanism for typical HO irrespective of the signal initiating the bone formation.
Kan
Lixin
L
Department of Neurology, Northwestern University Feinberg Medical School, Chicago, Illinois 60611-3008, USA. l-kan@northwestern.edu
Liu
Yijie
Y
McGuire
Tammy L
TL
Berger
Diana M Palila
DM
Awatramani
Rajeshwar B
RB
Dymecki
Susan M
SM
Kessler
John A
JA
D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism; D019070:Cell Lineage; D007107:Immune System / Q000276:immunology; D019426:Integrases / Q000378:metabolism; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008954:Models, Biological; D009132:Muscles / Q000473:pathology; D009999:Ossification, Heterotopic / Q000276:immunology / Q000473:pathology*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D012867:Skin / Q000473:pathology; D013234:Stem Cells / Q000473:pathology*
D055415:Bone Morphogenetic Protein 4; C045073:Cre recombinase; D019426:Integrases; D010751:Phosphopyruvate Hydratase