Inhibition of IL‐17 prevents the progression of traumatic heterotopic ossification
Autor: | Jing Zhu, Wei Wang, Feng Yuan, Cunyi Fan, Bing Tu, Bo Yu, Juehong Li |
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Rok vydání: | 2021 |
Předmět: |
Adult
Male IL‐17 Mice Young Adult Osteogenesis medicine Animals Humans Inducer Neutralizing antibody Pathological beta Catenin biology Chemistry Ossification Heterotopic Interleukin-17 Mesenchymal stem cell Antibodies Monoclonal Soft tissue Mesenchymal Stem Cells Original Articles Cell Biology Middle Aged medicine.disease Disease Models Animal trauma heterotopic ossification biology.protein Cancer research β‐catenin Molecular Medicine Original Article Female Heterotopic ossification Interleukin 17 Antibody Heterocyclic Compounds 3-Ring Signal Transduction |
Zdroj: | Journal of Cellular and Molecular Medicine |
ISSN: | 1582-4934 1582-1838 |
Popis: | 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. |
Databáze: | OpenAIRE |
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