Oridonin ameliorates inflammation-induced bone loss in mice via suppressing DC-STAMP expression  

作　　者：Bin-hua Zou Yan-hui Tan Wen-de Deng Jie-huang Zheng Qin Yang Min-hong Ke Zong-bao Ding Xiao-juan Li 

机构地区：[1]Laboratory of Anti-inflammatory and Immunomodulatory Pharmacology,School of Pharmaceutical Sciences,Southern Medical University,Guangzhou,510515,China [2]Guangdong Provincial Key Laboratory of New Drug Screening,School of Pharmaceutical Sciences,Southern Medical University,Guangzhou,510515,China

出　　处：《Acta Pharmacologica Sinica》2021年第5期744-754,共11页中国药理学报（英文版）

基　　金：This work was supported by Guangzhou Science and Technology Plan Project(201804010027);the National Natural Science Foundation of China(81773740,81073119).

摘　　要：Currently, dendritic cell-specific transmembrane protein (DC-STAMP), a multipass transmembrane protein, is considered as the master regulator of cell–cell fusion, which underlies the formation of functional multinucleated osteoclasts. Thus, DC-STAMP has become a promising target for osteoclast-associated osteolytic diseases. In this study, we investigated the effects of oridonin (ORI), a natural tetracyclic diterpenoid compound isolated from the traditional Chinese herb Rabdosia rubescens, on osteoclastogenesis in vivo and ex vivo. ICR mice were injected with LPS (5 mg/kg, ip, on day 0 and day 4) to induce inflammatory bone destruction. Administration of ORI (2, 10 mg·kg^(−1)·d^(−1), ig, for 8 days) dose dependently ameliorated inflammatory bone destruction and dramatically decreased DC-STAMP protein expression in BMMs isolated from LPS-treated mice. Treatment of preosteoclast RAW264.7 cells with ORI (0.78–3.125 μM) dose dependently inhibited both mRNA and protein levels of DC-STAMP, and suppressed the following activation of NFATc1 during osteoclastogenesis. Knockdown of DC-STAMP in RAW264.7 cells abolished the inhibitory effects of ORI on RANKL-induced NFATc1 activity and osteoclast formation. In conclusion, we show for the first time that ORI effectively attenuates inflammation-induced bone loss by suppressing DC-STAMP expression, suggesting that ORI is a potential agent against inflammatory bone diseases.

关 键 词：DC-STAMP OSTEOCLAST ORIDONIN NFATc1 inflammatory bone loss 

分 类 号：R285[医药卫生—中药学]