Inhibition of IL-17 prevents the progression of traumatic heterotopic ossification.

Abstract

Traumatic heterotopic ossification (HO) is the abnormal formation of bone in soft tissues as a consequence of injury. However, the pathological mechanisms leading to traumatic HO remain unknown. Here, we report that aberrant expression of IL‐17 promotes traumatic HO formation by activating β‐catenin signalling in mouse model. We found that elevated IL‐17 and β‐catenin levels are correlated with a high degree of HO formation in specimens from patients and HO animals. We also show that IL‐17 initiates and promotes HO progression in mice. Local injection of an IL‐17 neutralizing antibody attenuates ectopic bone formation in a traumatic mouse model. IL‐17 enhances the osteoblastic differentiation of mesenchymal stem cells (MSCs) by activating β‐catenin signalling. Moreover, inhibition of IL‐17R or β‐catenin signalling by neutralizing antibodies or drugs prevents the osteogenic differentiation of isolated MSCs and decreases HO formation in mouse models. Together, our study identifies a novel role for active IL‐17 as the inducer and promoter of ectopic bone formation and suggests that IL‐17 inhibition might be a potential therapeutic target in traumatic HO.