Heterotopic ossification (HO) is defined as the formation of bone inside soft tissue. Symptoms include joint stiffness, swelling, and pain. Apart from the inherited form, the common traumatic form occurs generally at sites of injury in damaged muscles and is often associated with brain injury. We investigated bone morphogenetic protein 9 (BMP9), which possesses a strong osteoinductive capacity, for its involvement in muscle HO physiopathology. We found that BMP9 had an osteoinductive influence on mouse muscle resident stromal cells by increasing their alkaline phosphatase activity and bone-specific marker expression. Interestingly, BMP9 induced HO only in damaged muscle while BMP2 promoted HO in skeletal muscle regardless of its state. The addition of the soluble form of the ALK1 protein (the BMP9 receptor) significantly inhibited the osteoinductive potential of BMP9 in cells and HO in damaged muscles. BMP9 should thus be considered as a candidate for involvement in HO physiopathology with its activity dependent on the skeletal muscle microenvironment. |