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

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

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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 ERα expression levels of hBMSC,and promoted osteogenic differ-entiation and bone formation.Mechanistically,via the ERα signaling 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 ERα in 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.

Rhizoma Drynariae-derived nanovesiclesBone marrow mesenchymal stem cellsBone targetingOsteogenic differentiationERα signalingNaringinBone morphogenetic protein 2Runt-related transcription factor 2

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

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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

Guangdong Engineering Research Center of Chinese Herbal-derived Vesicles,Guangzhou University of Chinese Medicine,Guangzhou 510006,China

Department of Laboratory Medicine,Nanfang Hospital,Southern Medical University,Guangzhou 510515,China

Guangdong Engineering and Technology Research Center for Rapid Diagnostic Biosensors,Nanfang Hospital,Southern Medical University,Guangzhou 510515,China

The Fifth Affiliated Hospital Sun Yat-sen University,Zhuhai 519000,China

Department of Blood Transfusion,Guangdong Heyou International Hospital,Foshan 528306,China

School of Pharmacy,Nanjing University of Chinese Medicine,Nanjing 210023,China

Guangdong Engineering and Technology Research Center for Rapid Diagnostic Bios

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国家自然科学基金国家自然科学基金国家自然科学基金science and Technology Projects in Liwan District,Guangzhou,Chinascience and Technology Projects in Liwan District,Guangzhou,ChinaYoung Talent Support Project of Guangzhou Association for Science and Technology,ChinaSpecial focus areas for General Universities in Guangdong Province,ChinaGuangdong Provincial Administration of Traditional Chinese Medicine Project,China

82174119819736338227422020230710202201009QT20230362022ZDZX201620233025

2024

10.1016/j.apsb.2024.02.005

药学学报(英文版)

药学学报(英文版)

CSTPCD
ISSN：
年,卷(期)：2024.14(5)
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