Skeletal characterization of an osteoblast-specific vitamin D receptor transgenic (ObVDR-B6) mouse model

Abstract

Background: Overexpression of the human vitamin D receptor (hVDR) transgene under control of the human osteocalcin promoter in FVB/N mice (OSVDR) was previously demonstrated to exhibit increased cortical and trabecular bone volume and strength due to decreased bone resorption and increased bone formation. An important question to address is whether the OSVDR bone phenotype persists on an alternative genetic background such as C57Bl6/J.

Methods: OSVDR mice (OSV3 line) were backcrossed onto the C57Bl6/J genetic background for at least 6 generations to produce OSVDR mice with 98.4% C57Bl6/J congenicity (ObVDR-B6 mice). Hemizygous male and female ObVDR-B6 and littermate wild-type (WT) mice were fed a standard laboratory chow diet and killed at 3, 9 and 20 weeks of age for analyses of biochemical and structural variables and dynamic indices of bone histomorphometry.

Results: At 9 weeks of age, both cortical and trabecular femoral bone volumes were increased in both male and female ObVDR-B6 mice, when compared to WT levels (P<0.05), without systemic changes to calciotropic parameters. The increase in femoral trabecular bone volume was associated with increase in MAR (P<0.01) and reduced osteoclast size (P<0.05). However, in female mice trabecular bone volume was unchanged in femoral metaphysis of 20 weeks mice and in vertebra both at 9 and 20 weeks of age. Increased cortical bone in both male and female ObVDR-B6 mice was due largely to increased periosteal expansion and was associated with increased cortical strength at 20 weeks of age.

Conclusion: Overexpression of the human VDR gene in mature osteoblasts of C57Bl6/J mice increases cortical and trabecular bone volumes and confirms the previous reports of increased bone in OSVDR mice on the FVB/N background. However, site-specific and gender-related differences in bone volume suggest that the effects of osteoblast-specific VDR overexpression are more complex than hitherto recognised.

Keywords: Bone mineral; Bone morphology; Vitamin D receptor.