Mechanisms involved in bone resorption regulated by vitamin D. Issue 177 (March 2018)

• Record Type: Journal Article
• Authors: Nakamichi, Yuko; Udagawa, Nobuyuki; Suda, Tatsuo; Takahashi, Naoyuki
• Is Part Of: Journal of steroid biochemistry and molecular biology. Issue 177(2017)
• Page Start: 70
• Page End: 76
• Publication Date: 2018-03
• Subjects: Vitamin D -- Osteoclasts -- Pro-resorptive -- Anti-resorptive -- Osteoblast lineage-specific VDR cKO -- Osteoclast-specific VDR cKO -- FGF23; Steroid hormones -- Periodicals; Biochemistry -- Periodicals; Hormones -- Periodicals; Molecular Biology -- Periodicals; Hormones stéroïdes -- Périodiques; Steroid hormones; Periodicals; 572.579
• DOI: 10.1016/j.jsbmb.2017.11.005
• Languages: English
• ISSNs: 0960-0760

Abstract

Highlights: Osteoblasts and osteocytes express VDR protein most abundantly among bone cells. Osteoclast-specific VDR knockout mice exhibit no discernible defects in bone. VDR in osteoblastic cells is involved in calcium metabolism and FGF23 production. Vitamin D implements pro- or anti-resorptive properties depending on protocols. Anti-resorptive effects in vivo are mediated by VDR in osteoblastic cells. 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)