Journal of Rehabilitation Research & Development (JRRD)

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Volume 51 Number 7, 2014
   Pages 1109 — 1118

Abstract — Novel mouse model of spinal cord injury-induced heterotopic ossification

Heejae Kang, BA;1 Alexis B. C. Dang, MD;1–2 Sunil K. Joshi, BA;1–2 Bernard Halloran, PhD;1,3 Robert Nissenson, PhD;1,3 Xia Zhang, MD;4 Jianan Li, MD;4 Hubert T. Kim, MD, PhD;1–2 Xuhui Liu, MD1–2*

1San Francisco Department of Veterans Affairs Medical Center, San Francisco, CA; Departments of 2Orthopaedic Surgery and 3Medicine, University of California at San Francisco, San Francisco, CA; 4Department of Rehabilitation Medicine, First Affiliate Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China

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. Microcomputed 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.

Key words: bone morphogenetic protein-2, heterotopic ossification, injury, microcomputed tomography, mouse model, muscle, rehabilitation, spinal cord injury, trauma, Veterans.


View HTML ¦ View PDF ¦ Contents Vol. 51, No.7

This article and any supplementary material should be cited as follows:
Kang H, Dang AB, Joshi SK, Halloran B, Nissenson R, Zhang X, Li J, Kim HT, Liu X. Novel mouse model of spinal cord injury-induced heterotopic ossification. J Rehabil Res Dev. 2014;51(7):1109–18.
http://dx.doi.org/10.1682/JRRD.2014.01.0019

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