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Diosmetin inhibits osteoclast formation and differentiation and prevents LPS‐induced osteolysis in mice
Author(s) -
Shao Siyuan,
Fu Fangsheng,
Wang Ziyi,
Song Fangming,
Li Chen,
Wu Zuoxing,
Ding Jiaxing,
Li Kai,
Xiao Yu,
Su Yiji,
Lin Xixi,
Yuan Guixin,
Zhao Jinmin,
Liu Qian,
Xu Jiake
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.27887
Subject(s) - rankl , osteoclast , osteolysis , bone resorption , cathepsin k , chemistry , downregulation and upregulation , microbiology and biotechnology , nf κb , osteoblast , activator (genetics) , cancer research , medicine , signal transduction , receptor , biochemistry , biology , in vitro , surgery , gene
Abstract Osteolytic bone diseases are closely linked to the over‐activation of osteoclasts and enhancement of bone resorption. It has become a major health issue in orthopedic practice worldwide. Inhibition of osteoclasts is proposed to be the main treatment for osteolytic disorders. Diosmetin (DIO) is a natural flavonoid with properties of antioxidant, anti‐infection, and antishock. The effect of DIO on osteoclast differentiation is poorly understood. In this study project, we found that DIO could inhibit osteoclastic formation induced by receptor activator of nuclear factor kappa‐B ligand (RANKL) in a dose‐dependent manner. The expression of the osteoclast differentiation marker genes, cathepsin K, nuclear factor of activated T‐cells 1 ( NFATc1 ), Acp5, Ctr, Atp6v0d2, and Mmp9 were also decreased by the treatment of DIO. In addition, DIO attenuated the formation of actin ring and the ability of bone resorption. Further, the western blotting showed that DIO inhibits the phosphorylation of the mitogen‐activated protein kinases signaling pathway induced by RANKL, accompanied by the downregulation of NFATc1 and c‐Fos expression. We also found that DIO could reduce the accumulation of reactive oxygen species (ROS) induced by RANKL. In vivo, the study revealed that DIO can significantly reduce LPS‐induced osteolysis in mice. Collectively, our study shows that DIO can inhibit osteoclast formation and activation, and could serve as a potential therapeutic drug for osteolytic bone diseases.