Cyclin G2 Suppresses Estrogen-Mediated Osteogenesis through Inhibition of Wnt/β-Catenin Signaling

被引:15
作者
Gao, Jinlan [1 ]
Liu, Qi [1 ]
Liu, Xing [1 ]
Ji, Chunyan [1 ]
Qu, Shengqiang [1 ]
Wang, Shusen [1 ]
Luo, Yang [1 ]
机构
[1] China Med Univ, Minist Educ, Key Lab Med Cell Biol, Res Ctr Med Genom,Key Lab Cell Biol,Minist Publ H, Shenyang, Peoples R China
来源
PLOS ONE | 2014年 / 9卷 / 03期
基金
中国国家自然科学基金;
关键词
HIGH BONE MASS; POSTMENOPAUSAL WOMEN; PHOSPHOINOSITIDE; 3-KINASE; NEGATIVE REGULATOR; SEX STEROIDS; EXPRESSION; DIFFERENTIATION; OSTEOPOROSIS; MARROW; TRANSCRIPTION;
D O I
10.1371/journal.pone.0089884
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Estrogen plays an important role in the maintenance of bone formation, and deficiency in the production of estrogen is directly linked to postmenopausal osteoporosis. To date, the underlying mechanisms of estrogen-mediated osteogenic differentiation are not well understood. In this study, a pluripotent mesenchymal precursor cell line C2C12 was used to induce osteogenic differentiation and subjected to detection of gene expressions or to manipulation of cyclin G2 expressions. C57BL/6 mice were used to generate bilateral ovariectomized and sham-operated mice for analysis of bone mineral density and protein expression. We identified cyclin G2, an unconventional member of cyclin, is involved in osteoblast differentiation regulated by estrogen in vivo and in vitro. In addition, the data showed that ectopic expression of cyclin G2 suppressed expression of osteoblast transcription factor Runx2 and osteogenic differentiation marker genes, as well as ALP activity and in vitro extracellular matrix mineralization. Mechanistically, Wnt/beta-catenin signaling pathway is essential for cyclin G2 to inhibit osteogenic differentiation. To the best of our knowledge, the current study presents the first evidence that cyclin G2 serves as a negative regulator of both osteogenesis and Wnt/beta-catenin signaling. Most importantly, the basal and 17 beta-estradiol-induced osteogenic differentiation was restored by overexpression of cyclin G2. These results taken together suggest that cyclin G2 may function as an endogenous suppressor of estrogen-induced osteogenic differentiation through inhibition of Wnt/beta-catenin signaling.
引用
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页数:9
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