Rhizoma Drynariae-derived nanovesicles reverse osteoporosis by potentiating osteogenic differentiation of human bone marrow mesenchymal stem cells via targeting ERα signaling  

作　　者：Qing Zhao Junjie Feng Fubin Liu Qianxin Liang Manlin Xie Jiaming Dong Yanfang Zou Jiali Ye Guilong Liu Yue Cao Zhaodi Guo Hongzhi Qiao Lei Zheng Kewei Zhao 

机构地区：[1]Guangzhou Key Laboratory of Chinese Medicine Research on Prevention and Treatment of Osteoporosis,the Third Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510378,China [2]Guangdong Engineering Research Center of Chinese Herbal-derived Vesicles,Guangzhou University of Chinese Medicine,Guangzhou 510006,China [3]Department of Laboratory Medicine,Nanfang Hospital,Southern Medical University,Guangzhou 510515,China [4]Guangdong Engineering and Technology Research Center for Rapid Diagnostic Biosensors,Nanfang Hospital,Southern Medical University,Guangzhou 510515,China [5]The Fifth Affiliated Hospital Sun Yat-sen University,Zhuhai 519000,China [6]Department of Blood Transfusion,Guangdong Heyou International Hospital,Foshan 528306,China [7]School of Pharmacy,Nanjing University of Chinese Medicine,Nanjing 210023,China

出　　处：《Acta Pharmaceutica Sinica B》2024年第5期2210-2227,共18页药学学报（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(Nos.82174119,81973633 and 82274220);Science and Technology Projects in Liwan District,Guangzhou(Nos.20230710 and 202201009,China);Young Talent Support Project of Guangzhou Association for Science and Technology(No.QT2023036,China);Special focus areas for General Universities in Guangdong Province(No.2022ZDZX2016,China);Guangdong Provincial Administration of Traditional Chinese Medicine Project(No.20233025,China).

摘　　要：Although various anti-osteoporosis drugs are available,the limitations of these therapies,including drug resistance and collateral responses,require the development of novel anti-osteoporosis agents.Rhizoma Drynariae displays a promising anti-osteoporosis effect,while the effective component and mechanism remain unclear.Here,we revealed the therapeutic potential of Rhizoma Drynariae-derived nanovesicles(RDNVs)for postmenopausal osteoporosis and demonstrated that RDNVs potentiated osteogenic differentiation of human bone marrow mesenchymal stem cells(hBMSCs)by targeting estrogen receptor-alpha(ERα).RDNVs,a natural product isolated from fresh Rhizoma Drynariae root juice by differential ultracentrifugation,exhibited potent bone tissue-targeting activity and anti-osteoporosis efficacy in an ovariectomized mouse model.RDNVs,effectively internalized by hBMSCs,enhanced proliferation and ERαexpression levels of hBMSC,and promoted osteogenic differentiation and bone formation.Mechanistically,via the ERαsignaling pathway,RDNVs facilitated mRNA and protein expression of bone morphogenetic protein 2 and runt-related transcription factor 2 in hBMSCs,which are involved in regulating osteogenic differentiation.Further analysis revealed that naringin,existing in RDNVs,was the active component targeting ERαin the osteogenic effect.Taken together,our study identified that naringin in RDNVs displays exciting bone tissue-targeting activity to reverse osteoporosis by promoting hBMSCs proliferation and osteogenic differentiation through estrogen-like effects.

关 键 词：Rhizoma Drynariae-derived nanovesicles Bone marrow mesenchymal stem cells Bone targeting Osteogenic differentiation ERαsignaling NARINGIN Bone morphogenetic protein 2 Runt-related transcription factor 2 

分 类 号：R735.9[医药卫生—肿瘤]