A frequent complication of severe brain and spine injuries in patients is the abnormal development of bones in muscles and joints of paralysed limbs. This extra skeletal bone formation, called heterotopic ossification, is extremely debilitating and painful and further increases patients’ dependence.
Due to the absence of animal models of heterotopic ossification following spinal cord injury, the mechanisms are unknown, and there is no treatment apart from surgical resection of heterotopic bones. Our laboratory has established the first mouse model of heterotopic ossification following spinal cord injury by combining spinal cord injury with a muscle inflammation. This unique model will be used to understand the mechanisms causing this complication and test treatments that could prevent it. The purpose of this study is three-fold: to identify the cells responsible for making bones in muscles, factors produced in response to spine disruption that initiate bone formation in muscles and to determine whether inflammation in the muscle is the event triggering this abnormal ossification.
The first results of this project have identified population muscle stem cells that are prone to osteogenic differentiation in vitro suggesting that the mesenchymal progenitors that differentiate into osteoblasts following spinal cord injuries are already present in healthy muscles. These results will be further tested in vivo.
This project aims to improve the treatment strategy of heterotopic ossification in patients with spinal cord or brain injury. Discoveries from this project will be directly translatable into the clinical trials to decrease of the incidence of heterotopic ossification. The results of the project will also have social significance as the financial and human costs of managing patients with spinal cord injuries.