Mechanisms involved in bone resorption regulated by vitamin D.

Abstract

Active forms of vitamin D enhance osteoclastogenesis in vitro and in vivo through the vitamin D receptor (VDR) in osteoblast-lineage cells consisting of osteoblasts and osteocytes. This pro-resorptive activity was evident basically with higher concentrations of active vitamin D than those expected in physiological conditions. Nevertheless, vitamin D compounds have been used in Japan for treating osteoporosis to increase bone mineral density (BMD). Of note, the increase in BMD by long-term treatment with pharmacological (=near-physiological) doses of vitamin D compounds was caused by the suppression of bone resorption. Therefore, whether vitamin D expresses pro-resorptive or anti-resorptive properties seems to be dependent on the treatment protocols. We established osteoblast lineage-specific and osteoclast-specific VDR conditional knockout (cKO) mice using Osterix-Cre transgenic mice and Cathepsin K-Cre knock-in mice, respectively. According to our observation using these cKO mouse lines, neither VDR in osteoblast-lineage cells nor that in osteoclasts played important roles for osteoclastogenesis and bone resorption at homeostasis. However, using our cKO lines, we observed that VDR in osteoblast-lineage cells, but not osteoclasts, was involved in the anti-resorptive properties of pharmacological doses of vitamin D compounds in vivo. Two different osteoblast-lineage VDR cKO mouse lines were reported. One is a VDR cKO mouse line using alpha 1, type I collagen (Col1a1)-Cre transgenic mice (here we call Col1a1-VDR-cKO mice) and the other is that using dentin matrix protein 1 (Dmp1)-Cre transgenic mice (Dmp1-VDR-cKO mice). Col1a1-VDR-cKO mice exhibited slightly increased bone mass due to lowered bone resorption. In contrast, Dmp1-VDR-cKO mice exhibited no difference in BMD in agreement with our results regarding Ob-VDR-cKO mice. Here we discuss contradictory results and multiple modes of actions of vitamin D in bone resorption in detail. (279 words).

• Authors: Yuko Nakamichi, Nobuyuki Udagawa, Tatsuo Suda, Naoyuki Takahashi
• Journal: The Journal of steroid biochemistry and molecular biology (J Steroid Biochem Mol Biol) Vol. 177 Pg. 70-76 (03 2018) ISSN: 1879-1220 [Electronic] England
• PMID: 29146302 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2017 Elsevier Ltd. All rights reserved.

Chemical References

• FGF23 protein, human
• Fgf23 protein, mouse
• Osteoprotegerin
• RANK Ligand
• Receptor Activator of Nuclear Factor-kappa B
• Receptors, Calcitriol
• Vitamins
• Vitamin D
• Fibroblast Growth Factor-23

Topics

• Animals
• Bone Resorption (drug therapy, metabolism)
• Fibroblast Growth Factor-23
• Humans
• Osteogenesis (drug effects)
• Osteoprotegerin (physiology)
• RANK Ligand (physiology)
• Receptor Activator of Nuclear Factor-kappa B (physiology)
• Receptors, Calcitriol (physiology)
• Vitamin D (analogs & derivatives, pharmacology, therapeutic use)
• Vitamins (pharmacology, therapeutic use)