title: Novel mouse model of spinal cord injury-induced heterotopic ossification.
abstract: Heterotopic ossification (HO) develops in about 20% to 30% of patients with spinal cord injury (SCI) and significantly impairs their rehabilitation. There is no effective prevention or treatment for this condition at this time. Our current understanding of its etiology and pathophysiology is limited partially due to the lack of clinically relevant animal models. In this study, we report a novel mouse model of SCI-induced HO by administering a subthreshold dose of bone morphogenetic protein (BMP)-2 to muscles in mice after SCI. Micro-computed tomography scanning showed that an intramuscular injection of 0.25 micrograms of BMP-2 causes significant HO in mice with SCI but not in control (sham surgery) mice. Our analysis of gene expression showed significantly increased BMP signaling in quadriceps following SCI, suggesting that BMP signaling may play a role in SCI-induced HO. Administering 0.25 micrograms of BMP-2 to the front arms of the mice with SCI also results in the development of significant HO but not in control mice. This suggests that SCI causes a systematic osteogenic effect, which is not limited to paralyzed limbs. This novel mouse model will serve as a powerful tool in exploring the molecular mechanisms of SCI-induced HO, which may lead to novel treatment for this disease.
authors.affiliation: San Francisco Department of Veterans Affairs Medical Center, San Francisco, CA;
authors.forename: Heejae
authors.initials: H
authors.lastname: Kang
authors.forename: Alexis B C
authors.initials: AB
authors.lastname: Dang
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Joshi
authors.forename: Bernard
authors.initials: B
authors.lastname: Halloran
authors.forename: Robert
authors.initials: R
authors.lastname: Nissenson
authors.forename: Xia
authors.initials: X
authors.lastname: Zhang
authors.forename: JianAn
authors.initials: J
authors.lastname: Li
authors.forename: Hubert T
authors.initials: HT
authors.lastname: Kim
authors.forename: Xuhui
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics; D004195:Disease Models, Animal; D015870:Gene Expression; D055427:Growth Differentiation Factor 2 / Q000235:genetics; D007273:Injections, Intramuscular; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009999:Ossification, Heterotopic / Q000139:chemically induced* / Q000000981:diagnostic imaging; D052097:Quadriceps Muscle; D012333:RNA, Messenger / Q000032:analysis*; D015398:Signal Transduction / Q000235:genetics; D013119:Spinal Cord Injuries / Q000150:complications*; D055114:X-Ray Microtomography
chemical_list: C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055419:Bone Morphogenetic Protein 7; D055427:Growth Differentiation Factor 2; D012333:RNA, Messenger
keywords: Veterans; bone morphogenetic protein-2; heterotopic ossification; injury; micro-computed tomography; mouse model; muscle; rehabilitation; spinal cord injury; trauma