Diosmetin inhibits osteoclast formation and differentiation and prevents LPS-induced osteolysis in mice

Siyuan Shao, Fangsheng Fu, Ziyi Wang, Fangming Song, Chen Li, Zuo xing Wu, Jiaxing Ding, Kai Li, Yu Xiao, Yiji Su, Xixi Lin, Guixin Yuan, Jinmin Zhao, Qian Liu, Jiake Xu

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)12701-12713
Number of pages13
JournalJournal of Cellular Physiology
Volume234
Issue number8
DOIs
Publication statusPublished - 1 Aug 2019

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Osteolysis
Osteoclasts
RANK Ligand
Bone
NFATC Transcription Factors
Bone Diseases
Bone Resorption
Chemical activation
Far-Western Blotting
Cathepsin K
diosmetin
Phosphorylation
Differentiation Antigens
Orthopedics
Mitogen-Activated Protein Kinases
Flavonoids
Actins
Reactive Oxygen Species
Down-Regulation
Antioxidants

Cite this

Shao, Siyuan ; Fu, Fangsheng ; Wang, Ziyi ; Song, Fangming ; Li, Chen ; Wu, Zuo xing ; Ding, Jiaxing ; Li, Kai ; Xiao, Yu ; Su, Yiji ; Lin, Xixi ; Yuan, Guixin ; Zhao, Jinmin ; Liu, Qian ; Xu, Jiake. / Diosmetin inhibits osteoclast formation and differentiation and prevents LPS-induced osteolysis in mice. In: Journal of Cellular Physiology. 2019 ; Vol. 234, No. 8. pp. 12701-12713.
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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.",
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author = "Siyuan Shao and Fangsheng Fu and Ziyi Wang and Fangming Song and Chen Li and Wu, {Zuo xing} and Jiaxing Ding and Kai Li and Yu Xiao and Yiji Su and Xixi Lin and Guixin Yuan and Jinmin Zhao and Qian Liu and Jiake Xu",
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Shao, S, Fu, F, Wang, Z, Song, F, Li, C, Wu, ZX, Ding, J, Li, K, Xiao, Y, Su, Y, Lin, X, Yuan, G, Zhao, J, Liu, Q & Xu, J 2019, 'Diosmetin inhibits osteoclast formation and differentiation and prevents LPS-induced osteolysis in mice' Journal of Cellular Physiology, vol. 234, no. 8, pp. 12701-12713. https://doi.org/10.1002/jcp.27887

Diosmetin inhibits osteoclast formation and differentiation and prevents LPS-induced osteolysis in mice. / Shao, Siyuan; Fu, Fangsheng; Wang, Ziyi; Song, Fangming; Li, Chen; Wu, Zuo xing; Ding, Jiaxing; Li, Kai; Xiao, Yu; Su, Yiji; Lin, Xixi; Yuan, Guixin; Zhao, Jinmin; Liu, Qian; Xu, Jiake.

In: Journal of Cellular Physiology, Vol. 234, No. 8, 01.08.2019, p. 12701-12713.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Diosmetin inhibits osteoclast formation and differentiation and prevents LPS-induced osteolysis in mice

AU - Shao, Siyuan

AU - Fu, Fangsheng

AU - Wang, Ziyi

AU - Song, Fangming

AU - Li, Chen

AU - Wu, Zuo xing

AU - Ding, Jiaxing

AU - Li, Kai

AU - Xiao, Yu

AU - Su, Yiji

AU - Lin, Xixi

AU - Yuan, Guixin

AU - Zhao, Jinmin

AU - Liu, Qian

AU - Xu, Jiake

PY - 2019/8/1

Y1 - 2019/8/1

N2 - 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.

AB - 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.

KW - diosmetin (DIO)

KW - MAPK

KW - nuclear factor of activated T-cells 1 (NFATc1)

KW - osteoclasts

KW - osteolysis

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