Targeted inhibition of osteoclastogenesis reveals the pathogenesis and therapeutics of bone loss under sympathetic neurostress

作     者：Bingdong Sui Jin Liu Chenxi Zheng Lei Dang Ji Chen Yuan Cao Kaichao Zhang Lu Liu Minyan Dang Liqiang Zhang Nan Chen Tao He Kun Xuan Fang Jin Ge Zhang Yan Jin Chenghu Hu Bingdong Sui;Jin Liu;Chenxi Zheng;Lei Dang;Ji Chen;Yuan Cao;Kaichao Zhang;Lu Liu;Minyan Dang;Liqiang Zhang;Nan Chen;Tao He;Kun Xuan;Fang Jin;Ge Zhang;Yan Jin;Chenghu Hu

作者机构：State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi International Joint Research Center for Oral DiseasesCenter for Tissue EngineeringSchool of StomatologyThe Fourth Military Medical UniversityXi'anChina Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint DiseasesSchool of Chinese MedicineHong Kong Baptist UniversityHong Kong SARChina Xi'an Key Laboratory of Stem Cell and Regenerative MedicineInstitute of Medical ResearchNorthwestern Polytechnical UniversityXianChina Xi'an Institute of Tssue Engineering and Regenerative MedicineXianChina Department of Biochemistry and Molecular BiologySchool of Basic Medical SciencesXi'an Jiaotong UniversityXi'anChina 

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

年 卷 期：2022年第14卷第4期

页      面：479-488页

核心收录：

学科分类：1001[医学-基础医学(可授医学、理学学位)] 100104[医学-病理学与病理生理学] 10[医学] 

基　　金：supported by grants from the National Natural Science Foundation of China(81870796,82170988,81930025 and 82100969) the General Research Funds from the Research Grants Council of Hong Kong SAR(12114416,12100918,12136616 and 12103519) the China Postdoctoral Science Foundation(2019M663986 and BX20190380) 

主　　题：osteoclast pathogenesis homeostasis 

摘      要：Sympathetic cues via the adrenergic signaling critically regulate bone homeostasis and contribute to neurostress-induced bone loss,but the mechanisms and therapeutics remain incompletely ***,we reveal an osteoclastogenesis-centered functionally important osteopenic pathogenesis under sympatho-adrenergic activation with characterized micro RNA response and efficient *** discovered that osteoclastic mi R-21 was tightly regulated by sympatho-adrenergic cues downstream theβ2-adrenergic receptor(β2AR)signaling,critically modulated osteoclastogenesis in vivo by inhibiting programmed cell death 4(Pdcd4),and mediated detrimental effects of both isoproterenol(ISO)and chronic variable stress(CVS)on ***,without affecting osteoblastic bone formation,bone protection against ISO and CVS was sufficiently achieved by a(D-Asp8)-lipid nanoparticle-mediated targeted inhibition of osteoclastic mi R-21 or by clinically relevant drugs to suppress ***,these results unravel a previously underdetermined molecular and functional paradigm that osteoclastogenesis crucially contributes to sympatho-adrenergic regulation of bone and establish multiple targeted therapeutic strategies to counteract osteopenias under stresses.