A Novel Diterpenoid Suppresses Osteoclastogenesis and Promotes Osteogenesis by Inhibiting Ifrd1-Mediated and IκBα-Mediated p65 Nuclear Translocation

Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research
Zi'ang XieShunwu Fan

Abstract

Osteoporosis develops because of impaired bone formation and/or excessive bone resorption. Although the pharmacological treatment of osteoporosis has been extensively developed, alternative treatments are still needed. Here, we showed that oridonin (ORI), a diterpenoid isolated from Rabdosia rubescens, can suppress osteoclastogenesis and enhance osteogenesis. ORI inhibited the receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclast formation and bone resorption through the inhibition of p65 nuclear translocation. ORI-induced inhibition of this translocation led to an increase in osteoblast differentiation and mineralization through the promotion of Smad1/Smad5 phosphorylation. Further analyses demonstrated that the inhibition of p65 nuclear translocation is due to the suppression of IκBα phosphorylation and the induced proteasomal degradation of interferon-related development regulator 1 (Ifrd1), a transcriptional corepressor that is involved in the suppression of NF-κB nuclear translocation. Moreover, mice treated with ORI at catabolic and anabolic windows showed a considerable attenuation of ovariectomy (OVX)-induced osteoporosis. Taken together, our findings reveal that ORI protects against OVX-indu...Continue Reading

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Citations

Dec 12, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Zhiwei JieZiang Xie
Jan 18, 2019·Journal of Cellular Physiology·Yexin WangShanyong Zhang
Mar 21, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Lin ZhengDengwei He
Sep 7, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Xuewu SunPeihua Shi
Oct 30, 2019·Mini Reviews in Medicinal Chemistry·Xu HuDahong Li
Aug 6, 2020·Acta Pharmacologica Sinica·Bin-Hua ZouXiao-Juan Li
Apr 11, 2018·Frontiers in Pharmacology·Chen-He ZhouHao-Bo Wu
Jan 21, 2021·Cell Death and Differentiation·Zeyu ZhengJian Chen
Apr 4, 2021·The Journal of Biological Chemistry·Yizhen HuangJianjun Ma
Sep 8, 2021·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Qingliang MaZhiwei Jie

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