Hederagenin protects mice against ovariectomy-induced bone loss by inhibiting RANKL-induced osteoclastogenesis and bone resorption

Kun Tian, Yuangang Su, Jiaxin Ding, Dairong Wang, Yunfei Zhan, Yicheng Li, Jiamin Liang, Xixi Lin, Fangming Song, Ziyi Wang, Jiake Xu, Qian Liu, Jinmin Zhao

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Abstract

Aims: Postmenopausal osteoporosis and other osteolytic bone diseases are often caused by the elevation in osteoclastogenesis and/or increased osteoclastic bone resorption, leading to excessive bone loss. Hederagenin (Hed) is a pentacyclic triterpenoid saponin extracted from various natural medicinal plants and exhibits numerous biological activities and may offer benefits against bone-related conditions. We evaluated the effects of Hed on osteoclast formation and bone resorption in vitro and the in vivo therapeutic benefits in the mouse model of ovariectomy (OVX)-induced bone loss. Main methods: In vitro, osteoclast formation were determined by TRAcp staining; bone resorption were examined using Hydroxyapatite resorption assay and Podosomal actin belt formation assay; Related molecular mechanisms were determined by western blot assay. Construction of OVX mice by bilateral oophorectomy to simulate bone loss in vivo. Key findings: In vitro cellular assays showed that Hed inhibited RANKL-induced osteoclast formation and osteoclast bone (hydroxyapatite) resorption as well as marker gene expression from BMM culture. Mechanistically, Hed attenuated RANKL-induced intracellular reactive oxygen species (ROS) production, and MAPK signaling pathway (ERK and p38) activation which curbed the downstream induction of c-Fos and NFATc1. Consistent with the in vitro findings, Hed administration effectively protected OVX mice from bone loss by reducing osteoclast number and activity on bone surface. Significance: Our data provided promising evidence for the potential use of Hederagenin in the treatment of osteoclast-mediated osteolytic bone diseases such as postmenopausal osteoporosis.

Original languageEnglish
Article number117336
JournalLife Sciences
Volume244
DOIs
Publication statusPublished - 1 Mar 2020

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