title: Mechanism of inhibitory action of eldecalcitol, an active vitamin D analog, on bone resorption in vivo.
abstract: Bone-resorbing osteoclasts differentiate from hematopoietic precursors under the strict regulation of bone-forming osteoblasts. Osteoblasts express two cytokines essentially required for osteoclastogenesis; macrophage-colony stimulating factor (M-CSF) and receptor activator of nuclear factor κB ligand (RANKL). Osteoblasts express constitutively M-CSF, and inducibly RANKL in response to bone resorption-stimulating factors. The active form of vitamin D3, 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3], is known to be a hormone which enhances RANKL expression in vitro. Nevertheless, Calcitoriol [1α,25(OH)2D3] and its prodrug, Alfacalcidol (1α-hydroxyvitamin D3) have been taken as therapeutic drugs in osteoporotic patients in Japan. In addition, Eldecalcitol [2β-(3-hydroxypropoxy)-1α,25(OH)2D3], a new analog of 1α,25(OH)2D3, was approved as a therapeutic agent for osteoporosis in Japan in 2011. Interestingly, those vitamin D compounds increased bone mineral density due to the suppression of bone resorption in vivo. We previously showed that cycle-arrested quiescent osteoclast precursors (QOPs) were the direct osteoclasts precursors in vivo. We then investigated effects of daily administration of Eldecalcitol on bone resorption in mice. Bone mineral density was increased through the suppression of RANKL expression in osteoblasts in mice treated with Eldecalcito. The number of QOPs remained unchanged in bone. These results suggest that a long-term exposure of osteoblasts to vitamin D compounds down-regulate RANKL expression. This article is part of a Special Issue entitled '15th Vitamin D Workshop'.
authors.affiliation: Institute for Oral Science, Matsumoto Dental University, 1780 Hiro-oka Gobara, Shiojiri, Nagano 399-0781, Japan. takahashinao@po.mdu.ac.jp
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001862:Bone Resorption / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D006801:Humans; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014807:Vitamin D / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D014807:Vitamin D; C547512:eldecalcitol