Isosteviol Derivative Inhibits Osteoclast Differentiation and Ameliorates Ovariectomy-Induced Osteoporosis

Huey En Tzeng, Po Hao Huang, Chun Hao Tsai, Gregory J. Tsay, Yi Ju Lee, Tsurng Juhn Huang, Tzu Hung Lin, Ying Ming Chiu, Yi Ying Wu

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Abstract

NC-8 (ent-16-oxobeyeran-19-N-methylureido) is an isosteviol-derived analogue with multiple biological effects, including anti-inflammation and anti-bacterial activities and inhibition of HBV viral surface antigen gene expression. In this study, we explored the effects of NC-8 on the formation of osteoclasts from RAW 264.7 cells. We found that NC-8 exerts the novel effect of inhibiting osteoclast-like cell formation. Our experiments showed that RANKL-induced ERK, p38, and JNK phosphorylation were inhibited by NC-8. An ovariectomy-induced osteoporosis animal model was used to examine the protective effects of oral treatment with NC-8. Serum analysis was used to examine markers of osteoblasts, osteoclasts, and renal and hepatic function in rats. Micro CT scanning and histological analysis were used to measure bone loss in ovariectomized rats. Oral administration of NC-8 effectively decreased excess bone resorption and significantly antagonized trabecular bone loss in ovariectomized rats. Serum analysis of C-terminal telopeptide of type-I collagen, an osteoclast marker, also showed that NC-8 administration inhibited excess bone resorption. Furthermore, serum analysis showed that renal and liver function were not affected by these doses of NC-8 during long-term treatment. Our results demonstrate that NC-8 inhibits osteoclast differentiation and effectively ameliorates ovariectomy-induced osteoporosis.

Original languageEnglish
Article number11190
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - Dec 1 2018

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Ovariectomy
Osteoclasts
Osteoporosis
Bone Resorption
Serum
Kidney
Viral Antigens
Liver
Surface Antigens
Osteoblasts
Oral Administration
Animal Models
Phosphorylation
isosteviol
Inflammation
Gene Expression
Bone and Bones
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

Isosteviol Derivative Inhibits Osteoclast Differentiation and Ameliorates Ovariectomy-Induced Osteoporosis. / Tzeng, Huey En; Huang, Po Hao; Tsai, Chun Hao; Tsay, Gregory J.; Lee, Yi Ju; Huang, Tsurng Juhn; Lin, Tzu Hung; Chiu, Ying Ming; Wu, Yi Ying.

In: Scientific Reports, Vol. 8, No. 1, 11190, 01.12.2018.

Research output: Contribution to journalArticle

Tzeng, Huey En ; Huang, Po Hao ; Tsai, Chun Hao ; Tsay, Gregory J. ; Lee, Yi Ju ; Huang, Tsurng Juhn ; Lin, Tzu Hung ; Chiu, Ying Ming ; Wu, Yi Ying. / Isosteviol Derivative Inhibits Osteoclast Differentiation and Ameliorates Ovariectomy-Induced Osteoporosis. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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