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Inhibition of IL-17 prevents the progression of traumatic heterotopic ossification |
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| Authors: | Bing Tu Bo Yu Wei Wang Juehong Li Feng Yuan Jing Zhu Cunyi Fan |
| Affiliation: | 1. Department of Orthopaedics, Shanghai Jiaotong University Affiliated Sixth People’s Hospital, Shanghai, China Department of Sports Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China Contribution: Data curation (lead), Investigation (lead), Methodology (lead);2. Department of Orthopaedics, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China Contribution: Funding acquisition (supporting), Investigation (equal), Project administration (equal);3. Department of Orthopaedics, Shanghai Jiaotong University Affiliated Sixth People’s Hospital, Shanghai, China Contribution: Data curation (supporting), Formal analysis (supporting);4. Department of Orthopaedics, Shanghai Jiaotong University Affiliated Sixth People’s Hospital, Shanghai, China Contribution: Investigation (supporting), Methodology (supporting), Project administration (supporting);5. Department of Orthopaedics, Shanghai Jiaotong University Affiliated Sixth People’s Hospital, Shanghai, China Department of Sports Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China Contribution: Conceptualization (supporting), Data curation (supporting);6. Department of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China;7. Department of Orthopaedics, Shanghai Jiaotong University Affiliated Sixth People’s Hospital, Shanghai, China |
| 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. |
| Keywords: | heterotopic ossification IL-17 trauma β-catenin |