title: A novel mouse model of trauma induced heterotopic ossification.
abstract: Severe soft tissue trauma is associated with heterotopic ossification (HO), the abnormal deposition of bone at extra-skeletal sites. The pathophysiology of the development of trauma-induced HO remains largely unknown due in part to the lack of appropriate animal models. In this study, we sought to develop a new trauma-induced HO mouse model using muscle impact injury combined with low dose BMP-2. BMP-2 at doses ranging from 0 to 2 µg was injected into quadriceps muscles of adult male C57/BL6 mice. Animals then received a one-time quadriceps impaction injury to mimic the trauma associated with severe injuries. HO was monitored using in vivo microCT scanning at 1, 2, 4, and 8 weeks after treatment. After trauma, the expression of BMP-2, -4, BMP receptor 1, SOX9 and RUNX2 were increased in muscle. Although little or no HO was observed in mice receiving 1 µg BMP-2, combining this dose with muscle trauma produced an abundance of HO. At higher doses of BMP-2, trauma did not augment mineral deposition. These results suggest that BMP-2 signaling can sensitize muscle to trauma-induced HO. They also provide the basis for a new model to study the pathogenesis of trauma-induced HO.
authors.affiliation: Department of Veterans Affairs, San Francisco Veterans Affairs Medical Center, 4150 Clement Street, San Francisco, CA, 94404; Department of Orthopedic Surgery, University of California at San Francisco, 500 Parnassus Avenue, San Francisco, CA, 94143.
authors.forename: Xuhui
authors.initials: X
authors.lastname: Liu
authors.forename: Heejae
authors.initials: H
authors.lastname: Kang
authors.forename: Mohammad
authors.initials: M
authors.lastname: Shahnazari
authors.forename: Hubert
authors.initials: H
authors.lastname: Kim
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
authors.forename: Olla
authors.initials: O
authors.lastname: Larm
authors.forename: Lars
authors.initials: L
authors.lastname: Adolfsson
authors.forename: Robert
authors.initials: R
authors.lastname: Nissenson
authors.forename: Bernard
authors.initials: B
authors.lastname: Halloran
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2; D001842:Bone and Bones / Q000378:metabolism; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009999:Ossification, Heterotopic / Q000139:chemically induced / Q000209:etiology*; D052097:Quadriceps Muscle / Q000187:drug effects / Q000293:injuries* / Q000378:metabolism
chemical_list: D055396:Bone Morphogenetic Protein 2
keywords: MicroCT; bone morphogenetic protein; heterotopic ossification; mouse model; trauma