Pectolinarigenin prevents bone loss in ovariectomized mice and inhibits RANKL-induced osteoclastogenesis via blocking activation of MAPK and NFATc1 signaling

Yu Xiao, Kai Li, Ziyi Wang, Fangsheng Fu, Siyuan Shao, Fangming Song, Jinmin Zhao, Weiwei Chen, Qian Liu, Jiake Xu

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Osteoporosis (OP) is a metabolic disease caused by multiple factors, which is characterized by a reduction of bone mass per unit volume and destruction of bone microstructure. Aberrant osteoclast function is the main cause of OP, therefore, regulating the differentiation and function of osteoclast is one of the treatment strategies for OP. Pectolinarigenin (PEC) is a medicinal implant isolated from Fragrant Eupatorium. Our experimental data showed that PEC was able to inhibit receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis in vitro, by tartrate-resistant acid phosphatase (TRAcP) staining, Fibrous actin ring formation, and hydroxyapatite resorption assays. In terms of mechanism, PEC inhibited the expression of the osteoclastogenesis-related gene, including cathepsin K (Ctsk), matrix metalloproteinase 9 (Mmp9), and TRAcP (Acp5). Western blot analysis demonstrated that PEC could significantly block the activation of RANKL-induced mitogen-activated protein kinase signaling cascades and was able to suppress the protein expression of nuclear factor of activated T-cells and c-Fos. Meanwhile, the intracellular reactive oxygen species levels were also reduced by PEC in a concentration-dependent manner. Further, PEC could prevent the ovariectomy-induced bone loss in vivo. Summarizing all, our data suggested that PEC inhibits osteoclast formation and function and RANKL signaling pathways, and thus could potentially be used in the treatment the osteoclast-related bone loss diseases.

Original languageEnglish
Pages (from-to)13959-13968
Number of pages10
JournalJournal of Cellular Physiology
Volume234
Issue number8
DOIs
Publication statusPublished - 1 Aug 2019

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