VDR in Osteoblast-Lineage Cells Primarily Mediates Vitamin D Treatment-Induced Increase in Bone Mass by Suppressing Bone Resorption.

Abstract

Long-term treatment with active vitamin D [1α,25(OH)2 D3 ] and its derivatives is effective for increasing bone mass in patients with primary and secondary osteoporosis. Derivatives of 1α,25(OH)2 D3 , including eldecalcitol (ELD), exert their actions through the vitamin D receptor (VDR). ELD is more resistant to metabolic degradation than 1α,25(OH)2 D3 . It is reported that ELD treatment causes a net increase in bone mass by suppressing bone resorption rather than by increasing bone formation in animals and humans. VDR in bone and extraskeletal tissues regulates bone mass and secretion of osteotropic hormones. Therefore, it is unclear what types of cells expressing VDR preferentially regulate the vitamin D-induced increase in bone mass. Here, we examined the effects of 4-week treatment with ELD (50 ng/kg/day) on bone using osteoblast lineage-specific VDR conditional knockout (Ob-VDR-cKO) and osteoclast-specific VDR cKO (Ocl-VDR-cKO) male mice aged 10 weeks. Immunohistochemically, VDR in bone was detected preferentially in osteoblasts and osteocytes. Ob-VDR-cKO mice showed normal bone phenotypes, despite no appreciable immunostaining of VDR in bone. Ob-VDR-cKO mice failed to increase bone mass in response to ELD treatment. Ocl-VDR-cKO mice also exhibited normal bone phenotypes, but normally responded to ELD. ELD-induced FGF23 production in bone was regulated by VDR in osteoblast-lineage cells. These findings suggest that the vitamin D treatment-induced increase in bone mass is mediated by suppressing bone resorption through VDR in osteoblast-lineage cells. © 2017 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.

• Authors: Yuko Nakamichi, Nobuyuki Udagawa, Kanji Horibe, Toshihide Mizoguchi, Yoko Yamamoto, Takashi Nakamura, Akihiro Hosoya, Shigeaki Kato, Tatsuo Suda, Naoyuki Takahashi
• Journal: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research (J Bone Miner Res) Vol. 32 Issue 6 Pg. 1297-1308 (Jun 2017) ISSN: 1523-4681 [Electronic] United States
• PMID: 28177161 (Publication Type: Journal Article)
• Copyright: © 2017 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.

Chemical References

• FGF23 protein, human
• Fgf23 protein, mouse
• Receptors, Calcitriol
• Vitamin D
• Fibroblast Growth Factor-23
• eldecalcitol

Topics

• Animals
• Bone Resorption (drug therapy, pathology)
• Bone and Bones (drug effects, pathology)
• Cell Lineage (drug effects)
• Fibroblast Growth Factor-23
• Gene Deletion
• Male
• Mice, Knockout
• Models, Biological
• Organ Size (drug effects)
• Osteoblasts (metabolism)
• Osteoclasts (drug effects, metabolism)
• Osteogenesis (drug effects)
• Phenotype
• Receptors, Calcitriol (genetics, metabolism)
• Vitamin D (analogs & derivatives, pharmacology, therapeutic use)