The roles of nuclear transcription factors in calcium homeostasis

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The physiologically active form of vitamin D3, 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3], is a nuclear hormone with pleiotropic action on the control of calcium homeostasis and bone formation, induction of cellular differentiation and apoptosis, inhibition of cellular proliferation, and other cellular signaling processes. The actions of the hormone are mediated by the vitamin D receptor (VDR), a transcription factor that is a nuclear receptor for 1α,25(OH)2D3 and a member of the nuclear receptor superfamily.A full-length cDNA for the rat kidney mitochondrial cytochrome P450 mixed function oxidase, 25-hydroxyvitamin D3-1α-hydroxylase (CYP27B1), was cloned from a vitamin D-deficient rat kidney cDNA library. The sequence analysis showed that CYP27B1 consisted of 2469 bp in length and contained an open reading frame encoding 501 amino acids. The expression of CYP27B1 mRNA was greatly increased in the kidney of hypocalcemic rats fed a low Ca diet. It is believed that the major regulator for … More renal CYP27B1 is parathyroid hormone (PTH) secreted in response to hypocalcemia. Administration of PTH into normocalcemic normal rats, however, did not induce at all renal expression of CYP27B1 mRNA. In contrast, a single injection of calcitonin (CT) dose- and time-dependently increased the expression of CYP27B1 mRNA in the kidney of normal rats. These results suggest that CT plays an important role in the maintenance of serum 1α,25(OH)2D3 under normocalcemic physiological conditions at least in rats.Osteoclast differentiation factor (ODF), a novel member of the TNF ligand family, is expressed as a membrane-associated protein by osteoblasts/stromal cells. The soluble form of ODF (sODF) induces the differentiation of osteoclast precursors into osteoclasts in the presence of M-CSF. A soluble form of RANK as well as osteoprotegerin/osteoclastogenesis inhibitory factor, a decoy receptor of ODF, blocked OGL formation and prevented the survival, multinucleation, and pit-forming activity of prefusion osteoclasts induced by sODF. These results suggest that ODF regulates not only osteoclast differentiation but also osteoclast function in mice through the receptor RANK. Less