β-Arrestin2缺失导致的小鼠骨重塑与骨组织GPER1表达下降关联  

Deficiency of β-arrestin 2 in mice.induced bone remodeling was associated with down-regulation of GPER1expression

作　　者：宋利革 刘红霞[1] 李晓雯[1] 慕开达[1] 林紫薇[1] 赵简[2] 王琛[1] 贾伟平[1] 

机构地区：[1]上海交通大学附属第六人民医院内分泌代谢科.上海市糖尿病研究所,上海市糖尿病重点实验室,200233 [2]中国科学院上海生命科学研究院,生物化学与细胞生物学研究所,200031

出　　处：《中华内分泌代谢杂志》2015年第10期897-901,共5页Chinese Journal of Endocrinology and Metabolism

基　　金：基金项目：2013国家自然科学基金专项资金项目（31340072）

摘　　要：目的探讨β-arrestin2缺失对小鼠骨重塑的影响及其发生机制。方法采用16、26、30周龄β-arrestin2敲除雌鼠和野生型雌鼠，通过双能X射线吸收法（DXA）检测其全身骨密度，微CT检测股骨微结构，RT—PCR检测骨形成、骨吸收相关因子和G蛋白耦联雌激素受体1的表达。结果β-Arrestin2敲除雌鼠在16周龄已出现全身骨密度降低，16、26、30周分别降低了8．10％、7．53％、8．56％。骨微结构检测显示3个周龄雌鼠骨体积分数均降低（分别为53．3％、49．4％、55．7％），骨小梁数量均减少（分别为53．2％、52．1％、49．3％），与各自的对照组野生型小鼠相比，差异均具有显著性（P〈0．05）。相反随着周龄的增长，敲除雌鼠骨小梁模式因子、间距、结构模型指数差异逐渐增大，至30周时与对照野生型小鼠相比差异统计学显著（分别增加了32．0％、54．3％、23．7％，P〈0．05）。胫骨RT-PCR检测显示护骨素．破骨细胞分化因子（RANKL）和G蛋白耦联雌激素受体1（GPER1）mRNA表达均降低，与对照组有明显差异（P〈0．05）。结论β-Arrestin2缺失导致的小鼠骨重塑与GPERl表达相关，提示其可能通过G蛋白耦联雌激素受体信号通路影响骨重塑。Objective To determine the role of β-arrestin 2 on bone mineral density and microarchitecture, and its underlying mechanisms. Methods Ex vivo dual-energy-X-ray-absorptiometry （ DXA ） was used to measure the total body bone mineral density （ BMD ） and miero-CT scan was performed on mouse femora from female mice of wild type（WT） and β-arrestin 2 knockout（KO） at 16, 26, 30 weeks of age. RT-PCR was applied for the mRNA expression. Results Started from 16 weeks of age, total body BMD and the bone volume/total volume （ BV/TV ） , trabeeular number（ Tb. N） in the femoral metaphysis of β-arrestin 2 KO female mice decreased dramatically. BMD decreased by 8.10%, 7.53%, 8.56%, BV/TV by 53.3%, 49.4%, 55.7% and Tb. N by 53.2%, 52. 1%, 49.3% at 16, 26, 30 weeks of age, respectively, compared with those in WT mice （ all P〈0.05）. In contrast, the trabecular pattern factor （ Tb. Pf）, trabecular separation （ Tb. Sp）, and structure model index （ SMI ） of the mice increased gradually with age, and reached statistically significant at age of 30 weeks（ increased by 32.0%, 54.3%, and 23.7%, respectively, all P〈0.05）. RT-PCR showed that mRNA expression levels of osteoprotegrin, RANKL, and G protein-coupled estrogen receptor 1 in tibia from β-arrestin 2 KO mice were significantly lower than those in WT mice. Conclusion The effects of β-arrestin 2 on bone remodeling might be associated with G protein-coupled estrogen receptorl signaling pathway.

关 键 词：β-Arrestin2 骨密度 骨微结构 护骨素 G蛋白耦联雌激素受体1 

分 类 号：R580[医药卫生—内分泌]