Deficiency Of ?-Arrestin2 In Mice–induced Decrease In Bone Mass Was Associated With Downregulation Of G Protein-coupled Estrogen Receptor 1 Expression

Objective To determine and explore the role of ?-arrestin2 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 u CT scan was performed on mouse femora from female mice of wild type(WT) and ?-arrestin2 knockout(KO) at 16, 26, 30 weeks of age. RT-PCR was applied for the m RNA 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 ?-arrestin2 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%, 2.1%, 49.3% at 16, 26, 30 weeks of age, respectively, compared with those in WT mice(all P < 0.05). Moreover, the trabecular pattern factor(Tb.Pf), trabecular separation(Tb.Sp) and structure model index(SMI) of the mice increased gradually with age, and reach statistic significantly at age of 30 weeks(increased by: 32.0%, 54.3% and 23.7%, respectively, all P < 0.05). RT-PCR showed that m RNA expression levels of OPG, RANKL and GPER1 in tibia from ?-arrestin2 KO mice was significantly lower than those in WT mice.Conclusion The effects of ?-arrestin2 on bone remodeling might be through the inhibition of G protein-coupled estrogen receptor1 signaling pathway.