β-Arrestin 2缺失导致的小鼠骨重塑与骨组织GPER1表达下降关联

摘要

目的 探讨β-arrestin 2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-arrestin 2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-Arrestin 2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-Arrestin 2缺失导致的小鼠骨重塑与GPER1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 micro-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),trabecular 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 receptor1 signaling pathway.