Interorgan communication in neurogenic heterotopic ossification: the role of brain-derived extracellular vesicles  

作　　者：Weicheng Lu Jianfei Yan Chenyu Wang Wenpin Qin Xiaoxiao Han Zixuan Qin Yu Wei Haoqing Xu Jialu Gao Changhe Gao Tao Ye Franklin R.Tay Lina Niu Kai Jiao 

机构地区：[1]Department of Stomatology,Tangdu Hospital&State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration&School of Stomatology,The Fourth Military Medical University,Xi’an,Shaanxi,China [2]State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration&National Clinical Research Center for Oral Diseases&Shaanxi Key Laboratory of Stomatology,School of Stomatology,The Fourth Military Medical University,Xi’an,Shaanxi,China [3]The Dental College of Georgia,Augusta University,Augusta,GA,USA

出　　处：《Bone Research》2024年第1期137-152,共16页骨研究（英文版）

基　　金：This work was supported by the National Nature Science Foundation of China grant 82170978(to K.J.);the Distinguished Young Scientists Funds of Shannxi Province 2021JC-34(to K.J.).

摘　　要：Brain-derived extracellular vesicles participate in interorgan communication after traumatic brain injury by transporting pathogens to initiate secondary injury.Inflammasome-related proteins encapsulated in brain-derived extracellular vesicles can cross the blood‒brain barrier to reach distal tissues.These proteins initiate inflammatory dysfunction,such as neurogenic heterotopic ossification.This recurrent condition is highly debilitating to patients because of its relatively unknown pathogenesis and the lack of effective prophylactic intervention strategies.Accordingly,a rat model of neurogenic heterotopic ossification induced by combined traumatic brain injury and achillotenotomy was developed to address these two issues.Histological examination of the injured tendon revealed the coexistence of ectopic calcification and fibroblast pyroptosis.The relationships among brain-derived extracellular vesicles,fibroblast pyroptosis and ectopic calcification were further investigated in vitro and in vivo.Intravenous injection of the pyroptosis inhibitor Ac-YVAD-cmk reversed the development of neurogenic heterotopic ossification in vivo.The present work highlights the role of brain-derived extracellular vesicles in the pathogenesis of neurogenic heterotopic ossification and offers a potential strategy for preventing neurogenic heterotopic ossification after traumatic brain injury.

关 键 词：NEUROGENIC OSSIFICATION PATHOGENESIS 

分 类 号：R651.1[医药卫生—外科学] R-332[医药卫生—临床医学]