机构：[1]The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China,广东省中医院[2]School of Biomedical Sciences, University of Western Australia, Perth, WA, Australia,[3]Department of Orthopedics, First People’s Hospital of Nanning, Fifth Affiliated Hospital of Guangxi Medical University, Nanning, China,[4]The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China,深圳市中医院深圳医学信息中心[5]Formula-Pattern Research Center, School of Traditional Chinese Medicine, Jinan University, Guangzhou, China
The extravagant osteoclast formation and resorption is the main cause of osteoporosis. Inhibiting the hyperactive osteoclastic resorption is considered as an efficient treatment for osteoporosis. Rhaponticin (RH) is a small molecule that has been reported to possess anti-inflammatory, anti-allergic, anti-fibrotic, and anti-diabetic activities. However, the influence of RH on osteoclasts differentiation and function is still unclear. To this end, an array of assays including receptor activator of nuclear factor kappa-Beta (NF-kappa B) ligand (RANKL) induced osteoclastogenesis, tartrate-resistant acidic phosphatase (TRAcP) staining, immunofluorescence, and hydroxyapatite resorption were performed in this study. It was found that RH had significant anti-catabolic effects by inhibiting osteoclastogenesis and bone resorption without cytotoxicity. Mechanistically, the expression of NADPH oxidase 1 (Nox1) was found to be suppressed and antioxidant enzymes including catalase, superoxide dismutase 2 (SOD-2), and heme oxygenase-1(HO-1) were enhanced following RH treatment, suggesting RH exhibited antioxidant activity by reducing the generation of reactive oxygen species (ROS) as well as enhancing the depletion of ROS. In addition, MAPKs, NF-kappa B, and intracellular Ca2+ oscillation pathways were significantly inhibited by RH. These changes led to the deactivation of osteoclast master transcriptional factor-nuclear factor of activated T cells 1 (NFATc1), as examined by qPCR and Western blot assay, which led to the decreased expression of downstream integrin beta 3, c-Fos, cathepsin K, and Atp6v0d2. These results suggested that RH could effectively suppress RANKL-regulated osteoclast formation and bone resorption. Therefore, we propose that RH can represent a novel natural small molecule for the treatment of osteoporosis by inhibiting excessive osteoclast activity.</p>
基金：
This study was supported in part by the Australian National
Health and Medical Research Council (NHMRC, Nos. 1107828,
1127156, 1163933), National Natural Science Foundation of
China Youth Fund (No. 81904091) and Fundamental Research
Funds for the Central Universities (No. 21619307).
第一作者机构：[1]The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China,[2]School of Biomedical Sciences, University of Western Australia, Perth, WA, Australia,
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Jianbo He,Kai Chen,Tiancheng Deng,et al.Inhibitory Effects of Rhaponticin on Osteoclast Formation and Resorption by Targeting RANKL-Induced NFATc1 and ROS Activity[J].FRONTIERS IN PHARMACOLOGY.2021,12:doi:10.3389/fphar.2021.645140.
APA：
Jianbo He,Kai Chen,Tiancheng Deng,Jiewei Xie,Kunjing Zhong...&Jiake Xu.(2021).Inhibitory Effects of Rhaponticin on Osteoclast Formation and Resorption by Targeting RANKL-Induced NFATc1 and ROS Activity.FRONTIERS IN PHARMACOLOGY,12,
MLA：
Jianbo He,et al."Inhibitory Effects of Rhaponticin on Osteoclast Formation and Resorption by Targeting RANKL-Induced NFATc1 and ROS Activity".FRONTIERS IN PHARMACOLOGY 12.(2021)
