Novel mouse model of spinal cord injury-induced heterotopic ossification
| Autor: | Sunil K. Joshi, Robert A. Nissenson, Heejae Kang, Alexis Dang, Xia Zhang, Jianan Li, Xuhui Liu, Bernard P. Halloran, Hubert T. Kim |
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| Rok vydání: | 2014 |
| Předmět: |
Male
medicine.medical_specialty Bone Morphogenetic Protein 7 Bone Morphogenetic Protein 2 Gene Expression Bone Morphogenetic Protein 4 Bone morphogenetic protein Injections Intramuscular Bone morphogenetic protein 2 Quadriceps Muscle Mice Internal medicine Gene expression Growth Differentiation Factor 2 medicine Animals RNA Messenger Spinal cord injury Spinal Cord Injuries business.industry Ossification Heterotopic Rehabilitation Sham surgery X-Ray Microtomography medicine.disease Pathophysiology Surgery Mice Inbred C57BL Disease Models Animal Endocrinology Heterotopic ossification business Intramuscular injection Signal Transduction |
| Zdroj: | Journal of Rehabilitation Research and Development. 51:1109-1118 |
| ISSN: | 1938-1352 0748-7711 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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