Abstract
The active form of vitamin D3, 1,25(OH)2D3, enhances osteoclastogenesis through the vitamin D receptor (VDR) in osteoblastic cells. This proresorptive activity was detected only with high doses of 1,25(OH)2D3 in vivo and in cultures in vitro in the presence of osteoblastic cells. In contrast, pharmacological doses of 1,25(OH)2D3 and its analogs suppressed bone resorption in vivo. A number of investigators including us inactivated the VDR gene in osteoblast precursors, osteoblasts, osteocytes, chondrocytes, osteoclast precursors, and osteoclasts in mice. VDR in osteoblastic cells (osteoblasts and osteocytes), but not osteoclast lineage cells, was essential for the proresorptive properties of high doses of 1,25(OH)2D3, which led to hypercalcemia associated with soft tissue calcification. Moreover, VDR in osteoblastic cells was involved in the antiresorptive properties of pharmacological doses of vitamin D compounds in vivo. However, under physiological (=basal) conditions, the 1,25(OH)2D3-VDR system in osteoblastic cells, chondrocytes, or in osteoclast lineage cells does not appear to be a major regulator of osteoclastogenesis. This chapter summarizes the phenotypes of osteoclast lineage, osteoblast lineage, and chondrocyte-specific VDR conditional knockout mice and the role of osteoblastic cell-expressed VDR in vitamin D-regulated bone resorption.
Published Version
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