Deleting Rac1 improves vertebral bone quality and resistance to fracture in a murine ovariectomy model
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : J. K. R. S. Magalhaes & M. D. Grynpas & T. L. Willett & M. Glogauer
- چاپ و سال / کشور: 2010
Description
Summary The roles of Rac1 and Rac2 in regulating osteoclast-mediated bone quality in postmenopausal osteoporosis were evaluated using an ovariectomized murine model. Animals' bone composition and architecture were evaluated. Our results demonstrate that the deletion of Rac1 increases vertebral bone quality compared to wild-type bones in an ovariectomized model. Introduction To determine the roles of the Rho family small GTPases Rac1 and Rac2 in regulating osteoclast-mediated bone quality in a model of postmenopausal osteoporosis. Methods Twelve-month-old female mice from three genotypes— wild type (WT), Rac1 null (LysM.Rac1 KO), and Rac2 null (Rac2KO)—were studied in control and ovariectomized groups (mice previously ovariectomized at 4 months of age). Animals were sacrificed at 12 months of age, and the femora and vertebrae were harvested for mechanical testing, bone densitometry, micro-computed tomography, and histomorphometric analyses to evaluate bone mineralization and architecture. The results were compared between groups using ANOVA and LSD post-hoc tests. Results We observed that LysM.Rac1 KO mice showed higher vertebral bone mineral density compared to WT in both control and ovariectomized groups. Consistent with this finding, LysM.Rac1 KO vertebrae showed increased resistance to fracture and increased trabecular connectivity compared to WT in both groups. Micro-CT analysis revealed that Rac2KO ovariectomized vertebrae have more trabecular bone compared to WT and LysM.Rac1 KO, but this did not translate into increased fracture resistance. Conclusion Our results demonstrate that the deletion of Rac1 increases vertebral bone quality compared to WT bones in a postmenopausal osteoporosis model.
Osteoporos Int (2011) 22:1481–1492 DOI 10.1007/s00198-010-1355-6 Received: 16 February 2010 / Accepted: 6 July 2010 / Published online: 4 August 2010
