Abstract
1α,25-Dihydroxy vitamin D3 [1,25(OH)2D3] acts on cells through traditional steroid hormone receptor-mediated gene transcription and by initiating rapid membrane-associated signaling pathways. Two receptors have been implicated in rapid signaling by 1,25(OH)2D3, the classical nuclear vitamin D receptor (VDR) and the more recently identified protein disulfide isomerase, family A, member 3 (Pdia3). Our lab along with other groups has established various tools to investigate the role of these two receptors, including gene knock-out, conditional knock-out, silencing, and over-expression in various model systems (growth plate chondrocytes, osteoblastic cells, chick intestinal epithelial cells, mouse embryoid bodies, extracellular matrix vesicles and isolated cell membranes). The data demonstrate the requirement for Pdia3 in 1,25(OH)2D3 induced phospholipase A2 (PLA2) and protein kinase C (PKC) activation and downstream responses. Pdia3+/- heterozygote mice also exhibit both cartilage and bone defects. VDR is present on the plasma membrane and one VDR-/- mouse strain lacks transcaltachia, although 1,25(OH)2D3 induced PKC activation and transcaltachia are not affected in another VDR-/- mouse strain. In the context of osteoblast differe...Continue Reading
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