β-Arrestin2缺失导致的小鼠骨量减少与骨组织G蛋白偶联雌激素受体1表达下降关联

发布时间：2018-12-20 07:55

【摘要】：目的:β-arrestin2是一种转接器蛋白,与G蛋白偶联受体结合,参与发挥多种生物学效应。本研究的目的是探讨β-arrestin2缺失对小鼠骨量的影响及其可能发生机理。方法:采用16,26,30周龄β-arrestin2敲除雌鼠和野生型雌鼠。小鼠通过腹腔注射1%戊巴比妥进行麻醉,利用双能X线吸收仪(Dual-energy-X-ray-absorptiometry,DXA)检测敲除和野生型鼠全身骨密度,微型计算机断层扫描技术(Micro-computed tomography,u CT)检测股骨微结构,RT-PCR检测胫骨骨形成、骨吸收相关因子和G蛋白偶联雌激素受体1(GPER1)的m RNA表达。结果:β-Arrestin2敲除雌鼠在16周龄开始出现全身骨密度降低,分别于16、26、30周降低了8.10%、7.53%、8.56%。u CT骨微结构检测显示上述三个周龄鼠骨体积分数,和骨小梁数量均较野生型鼠减少(骨体积分数:分别下降53.3%、49.4%和55.7%;骨小梁数量:分别下降53.2%、52.1%和49.3%),与各自的对照组野生型小鼠相比,差异均具有统计学显著性(all P0.05)。同时,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周时与对照野生小鼠相比达到统计学显著差异(分别增加了32.0%、54.3%、23.7%)(all P0.05)。胫骨组织RT-PCR检测显示护骨素(OPG),破骨细胞分化因子(RANKL)和GPER1m RNA表达均降低,与对照组有明显差异(P0.05)。结论:β-Arrestin2缺失导致小鼠骨重塑、骨量下降,该改变与GPER1表达下降相关,提示β-arrestin2缺失对小鼠骨代谢的影响可能通过G蛋白偶联雌激素受体信号通路。
[Abstract]:Aim: 尾-arrestin2 is a type of protein that binds to G protein and plays a variety of biological effects. The aim of this study was to investigate the effect of 尾-arrestin2 deletion on bone mass in mice and its possible mechanism. Methods: 尾-arrestin2 knockout female and wild type female were used. Mice were anesthetized by intraperitoneal injection of 1% pentobarbital. Bone mineral density (BMD) of knockout and wild-type mice was measured by dual energy X-ray absorptiometry (Dual-energy-X-ray-absorptiometry,DXA) and Micro-computed tomography,. Microstructures of femur were detected by u CT), bone formation of tibia, bone resorption related factor and m RNA expression of G protein-coupled estrogen receptor 1 (GPER1) were detected by RT-PCR. Results: the bone mineral density of 尾-Arrestin2 knockout female rats began to decrease at the age of 16 weeks, and the bone mass fraction of the three week old rats was decreased by 8.10% 7.53 and 8.56% at 162630 weeks, respectively. The results showed that the bone volume fraction of the three weeks old rats mentioned above was lower than that of the control group. The number of trabeculae and bone trabeculae were decreased (bone volume fraction: 53.3%, 49.4% and 55.7%, respectively); The number of trabeculae decreased by 53.1% and 49.3%, respectively, compared with the control group, the difference was statistically significant (all P0.05). At the same time, with the increase of age, the differences of trabecular model factors, spacing and structural model index increased gradually, and at 30 weeks the difference was statistically significant compared with the control wild mice (increased 32.0% and 54.3%, respectively). 23.7%) (all (P0.05). The expression of osteoclast differentiation factor (RANKL) and osteoclast differentiation factor (GPER1m RNA) in osteoclast of osteoprotegerin (OPG),) was significantly lower than that in the control group (P0.05). Conclusion: 尾-Arrestin2 deficiency can induce bone remodeling and decrease of bone mass in mice. This change is related to the decrease of GPER1 expression, suggesting that the effect of 尾-arrestin2 deletion on bone metabolism may be mediated by G protein-coupled estrogen receptor signaling pathway.
【学位授予单位】：上海交通大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R580

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