Acacetin inhibits RANKL-induced osteoclastogenesis and LPS-induced bone loss by modulating NFATc1 transcription

Mingchao Jin; Jiangbo Nie; Juli Zhu; Jing Li; Tianshun Fang; Juntao Xu; Xuesheng Jiang; Zhuo Chen; Jianyou Li; Fengfeng Wu

doi:10.1016/j.bbrc.2021.10.066

Acacetin inhibits RANKL-induced osteoclastogenesis and LPS-induced bone loss by modulating NFATc1 transcription

Biochem Biophys Res Commun. 2021 Oct 30:583:146-153. doi: 10.1016/j.bbrc.2021.10.066. Online ahead of print.

Authors

Mingchao Jin¹, Jiangbo Nie², Juli Zhu³, Jing Li⁴, Tianshun Fang¹, Juntao Xu³, Xuesheng Jiang¹, Zhuo Chen¹, Jianyou Li⁵, Fengfeng Wu⁶

Affiliations

¹ Department of Orthopedics, Huzhou Central Hospital, Affiliated Huzhou Hospital, Zhejiang University School of Medicine, NO.1558, Third Ring North Road, Huzhou, 313000, Zhejiang, China.
² Department of Orthopedics, Huzhou Central Hospital, Affiliated Huzhou Hospital, Zhejiang University School of Medicine, NO.1558, Third Ring North Road, Huzhou, 313000, Zhejiang, China. Electronic address: 21918401@zju.edu.cn.
³ Department of Orthopedics, Huzhou Traditional Chinese Medicine Hospital, Affiliated to Zhejiang Chinese Medical University, NO.315, South Street, Huzhou, 313000, Zhejiang, China.
⁴ Department of Physiology, Huzhou University, NO.759, Second Ring East Road, Huzhou, 313000, Zhejiang, China.
⁵ Department of Orthopedics, Huzhou Central Hospital, Affiliated Huzhou Hospital, Zhejiang University School of Medicine, NO.1558, Third Ring North Road, Huzhou, 313000, Zhejiang, China. Electronic address: ljywn1977@126.com.
⁶ Department of Orthopedics, Huzhou Central Hospital, Affiliated Huzhou Hospital, Zhejiang University School of Medicine, NO.1558, Third Ring North Road, Huzhou, 313000, Zhejiang, China. Electronic address: wufengfeng@zju.edu.cn.

PMID: 34763194
DOI: 10.1016/j.bbrc.2021.10.066

Abstract

Osteolytic disorders are characterized by impaired bone volume and trabecular structure that leads to severe fragility fractures. Studies have shown that excessive osteoclast activity causes impaired bone microstructure, a sign of osteolytic diseases such as osteoporosis. Approaches of inhibiting osteoclastogenesis and bone resorption specifically could prevent osteoporosis and other osteolytic disorders. Acacetin is a potent molecule extracted from plants with anti-cancer and anti-inflammatory bioactivities. Here, we demonstrated, for the first time, that acacetin repressed osteoclastogenesis, formation of F-actin rings, bone resorption activity, and osteoclast-related gene expression in vitro through modulating ERK, P38, and NF-κB signaling pathways and preventing expression of NFATc1. Micro-CT and H & E staining results indicated that acacetin alleviated LPS-induced osteolysis in vivo. Overall, our findings suggested that acacetin could help to prevent osteoporosis and other osteoclast-related osteolytic disorders.

Keywords: Acacetin; NFATc1; Osteoclast; Osteolysis; RANKL.