Galangin mitigates glucocorticoid-induced osteoporosis by activating autophagy of BMSCs via triggering the PKA/CREB signaling pathway  

作　　者：Chenying Zeng Shan Wang Huimin Gu Fenglei Chen Ziming Wang Jinteng Li Zhongyu Xie Pei Feng Huiyong Shen Yanfeng Wu 

机构地区：[1]Center for Biotherapy,Eighth Affiliated Hospital of Sun Yat-sen University,Shenzhen 518033,China [2]Department of Orthopedics,Eighth Affiliated Hospital of Sun Yat-sen University,Shenzhen 518033,China [3]Department of Orthopedics,Sun Yat-sen Memorial Hospital of Sun Yat-sen University,Guangzhou 510120,China

出　　处：《Acta Biochimica et Biophysica Sinica》2023年第8期1275-1287,共13页生物化学与生物物理学报（英文版）

基　　金：supported by the grants from the National Natural Science Foundation of China(Nos.82172349 and 82172385);the Shenzhen Key Laboratory of Ankylosing Spondylitis(No.ZDSYS20190902092851024).

摘　　要：Glucocorticoid-induced osteoporosis(GIOP),one of the most common and serious adverse effects associated with glucocorticoid administration,manifests as decreased bone formation and increased bone resorption,eventually culminating in bone loss.Galangin(GAL)is a flavonoid extracted from the medicinal herbal galangal that possesses a variety of pharmacological activities and can inhibit osteoclastogenesis.However,the effects of GAL on GIOP remain unclear.Our study aims to explore the effects of GAL on GIOP in mice and the underlying mechanism.Our results show that GAL markedly mitigates the severity of dexamethasone(Dex)-induced osteoporosis in mice and potentiates osteogenic differentiation in mouse bone marrow-derived mesenchymal stem cells(BMSCs).Furthermore,GAL also significantly counteracts Dex-mediated suppression of osteogenic differentiation and autophagy in human BMSCs.GAL augments PKA/CREB-mediated autophagic flux in BMSCs and the bones of osteoporotic mice.GAL-mediated osteogenic differentiation in Dex-treated BMSCs is significantly decreased by the PKA inhibitor H89 and autophagy inhibitor 3-methyladenine.Collectively,our data indicate that GAL can ameliorate GIOP,partly by augmenting the mineralization of BMSCs by potentiating PKA/CREB-mediated autophagic flux,highlighting its potential therapeutic use in treating glucocorticoid-related osteoporosis.

关 键 词：GALANGIN glucocorticoid-induced osteoporosis DEXAMETHASONE BMSC AUTOPHAGY 

分 类 号：R681[医药卫生—骨科学]