PMID- 26343450 OWN - NLM STAT- MEDLINE DCOM- 20170614 LR - 20171207 IS - 1879-1220 (Electronic) IS - 0960-0760 (Linking) VI - 164 DP - 2016 Nov TI - Skeletal characterization of an osteoblast-specific vitamin D receptor transgenic (ObVDR-B6) mouse model. PG - 331-336 LID - S0960-0760(15)30046-7 [pii] LID - 10.1016/j.jsbmb.2015.08.009 [doi] AB - 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. CI - Crown Copyright (c) 2015. Published by Elsevier Ltd. All rights reserved. FAU - Triliana, Rahma AU - Triliana R AD - Faculty of Medicine, Islamic University of Malang, Malang, East Java 65144 Indonesia; School of Medicine, Faculty of Health Science, The University of Adelaide, Adelaide, 5000 SA, Australia. FAU - Lam, Nga N AU - Lam NN AD - School of Medicine, Faculty of Health Science, The University of Adelaide, Adelaide, 5000 SA, Australia. FAU - Sawyer, Rebecca K AU - Sawyer RK AD - School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, 5001 SA, Australia. FAU - Atkins, Gerald J AU - Atkins GJ AD - Centre for Orthopaedics and Trauma Research, The University of Adelaide, Adelaide, 5000 SA, Australia. FAU - Morris, Howard A AU - Morris HA AD - School of Medicine, Faculty of Health Science, The University of Adelaide, Adelaide, 5000 SA, Australia; School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, 5001 SA, Australia. FAU - Anderson, Paul H AU - Anderson PH AD - School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, 5001 SA, Australia. Electronic address: paul.anderson@unisa.edu.au. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150904 PL - England TA - J Steroid Biochem Mol Biol JT - The Journal of steroid biochemistry and molecular biology JID - 9015483 RN - 0 (Receptors, Calcitriol) RN - 0 (VDR protein, human) RN - 104982-03-8 (Osteocalcin) SB - IM MH - Animals MH - Bone Density MH - Bone Resorption/genetics/metabolism/physiopathology MH - Crosses, Genetic MH - Female MH - Femur/anatomy & histology/*metabolism MH - Gene Expression MH - Humans MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Osteoblasts/cytology/*metabolism MH - Osteocalcin/*genetics/metabolism MH - Osteoclasts/cytology/*metabolism MH - Osteogenesis/genetics MH - Promoter Regions, Genetic MH - Receptors, Calcitriol/*genetics/metabolism MH - Transgenes OTO - NOTNLM OT - Bone mineral OT - Bone morphology OT - Vitamin D receptor EDAT- 2015/09/08 06:00 MHDA- 2017/06/15 06:00 CRDT- 2015/09/08 06:00 PHST- 2015/06/15 00:00 [received] PHST- 2015/08/05 00:00 [revised] PHST- 2015/08/11 00:00 [accepted] PHST- 2015/09/08 06:00 [pubmed] PHST- 2017/06/15 06:00 [medline] PHST- 2015/09/08 06:00 [entrez] AID - S0960-0760(15)30046-7 [pii] AID - 10.1016/j.jsbmb.2015.08.009 [doi] PST - ppublish SO - J Steroid Biochem Mol Biol. 2016 Nov;164:331-336. doi: 10.1016/j.jsbmb.2015.08.009. Epub 2015 Sep 4.