Mechanisms and Treatments of Heterotopic Ossification Following Spinal Cord Injuries
Technical Report,30 Sep 2015,29 Sep 2016
The University of Queensland Brisbane Australia
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Neurological heterotopic ossification NHO is a frequent complication of spinal cord injuries. NHO manifests as abnormal ossification of soft tissues near joints. NHO is debilitating, causing pain, joint deformation, ankylosis and vascular and nerve compression. The mechanisms leading to NHO are unknown and the only effective treatment is surgical resection. To elucidate NHO pathophysiology we have developed the first animal model of NHO in genetically unmodified mice. This model shows that formation of NHO requires the combined insult of SCI and soft tissue damage and inflammation via macrophages. To further elucidate the mechanisms driving NHO we treated SCI mice with the TNF- antagonist etanercept or the CSF-1receptor kinase inhibitor GW2580 preventative modality. NHO volumes were measured by CT 10 days after surgery and confirmed that treatment of mice with either etanercept or GW2580 results in a significant reduction in NHO bone volume 30and 37 reduction respectively. Finally we confirmed that conditional deletion of the Hif1a gene in myeloid cells which impairs M1 macrophage polarization significantly enhanced NHO formation by 47 after SCI and muscle injury. Overall our data suggests that targeting macrophages andor macrophage mediated inflammation may serve as viable therapies for the treatment of NHO.
- Medicine and Medical Research