TY - JOUR AU - Zou Bin-hua AU - Tan Yan-hui AU - Deng Wen-de AU - Zheng Jie-huang AU - Yang Qin AU - Ke Min-hong AU - Ding Zong-bao AU - Li Xiao-juan PY - 2021 TI - Oridonin ameliorates inflammation-induced bone loss in mice via suppressing DC-STAMP expression JF - Acta Pharmacologica Sinica; Vol 42, No 5 (May 2021): Acta Pharmacologica Sinica Y2 - 2021 KW - N2 - 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. UR - http://www.chinaphar.com/article/view/10317