Sema3A secreted by sensory nerve induces bone formation under mechanical loads

作     者：Hongxiang Mei Zhengzheng Li Qinyi Lv Xingjian Li Yumeng Wu Qingchen Feng Zhishen Jiang Yimei Zhou Yule Zheng Ziqi Gao Jiawei Zhou Chen Jiang Shishu Huang Juan Li Hongxiang Mei;Zhengzheng Li;Qinyi Lv;Xingjian Li;Yumeng Wu;Qingchen Feng;Zhishen Jiang;Yimei Zhou;Yule Zheng;Ziqi Gao;Jiawei Zhou;Chen Jiang;Shishu Huang;Juan Li

作者机构：State Key Laboratory of Oral Diseases&National Center for Stomatology&National Clinical Research Center for Oral Diseases&West China Hospital of StomatologySichuan UniversityChengduChina Department of Orthopedic Surgery and Orthopedic Research InstituteWest China HospitalSichuan UniversityChengduChina 

出 版 物：《International Journal of Oral Science》 (国际口腔科学杂志（英文版）)

年 卷 期：2024年第16卷第1期

页      面：62-72页

核心收录：

学科分类：1003[医学-口腔医学] 100302[医学-口腔临床医学] 10[医学] 

基　　金：supported in part by National Natural Science Foundation of China(32271364 & 31971240) Interdisciplinary innovation project from West China Hospital of Stomatology, Sichuan University(RD-03-202305) 

主　　题：Sema3A formation overload 

摘      要：Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling. Here, we focused on the role of Semaphorin 3A(Sema3A), expressed by sensory nerves, in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement(OTM) model. Firstly, bone formation was activated after the 3rd day of OTM,coinciding with a decrease in sensory nerves and an increase in pain threshold. Sema3A, rather than nerve growth factor(NGF),highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM. Moreover, in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells(hPDLCs) within 24 ***, exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload. Mechanistically, Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway, maintaining mitochondrial dynamics as mitochondrial fusion. Therefore, Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation, both as a pain-sensitive analgesic and a positive regulator for bone formation.