The roles of nuclear transcription factors in calcium homeostasis

维生素D3的生理活性形式1α，25-二羟基维生素D3 [1α，25（OH）2D 3]是一种核激素，对钙稳态和骨形成的控制、细胞分化和凋亡的诱导、细胞增殖的抑制以及其他细胞信号传导过程具有多效性作用。从维生素D缺乏大鼠肾脏cDNA文库中克隆了大鼠肾脏线粒体细胞色素P450混合功能氧化酶25-羟基维生素D3-1α-羟化酶（CYP 27 B1）的全长cDNA。序列分析表明，CYP 27 B1基因全长2469 bp，开放阅读框编码501个氨基酸。低钙组大鼠肾脏CYP 27 B1 mRNA表达显著增加。据信， ...更多信息 肾脏CYP 27 B1是对低钙血症作出反应而分泌的甲状旁腺激素（PTH）。然而，将PTH给药至正常血钙的正常大鼠中，根本不诱导肾脏CYP 27 B1 mRNA的表达。相反，单次注射降钙素（CT）的剂量和时间依赖性增加CYP 27 B1 mRNA在正常大鼠肾脏的表达。破骨细胞分化因子（ODF）是TNF配体家族的一个新成员，是成骨细胞/基质细胞表达的一种膜结合蛋白。可溶形式的ODF（sODF）在M-CSF存在下诱导破骨细胞前体分化成破骨细胞。RANK的可溶性形式以及骨保护素/破骨细胞生成抑制因子（ODF的诱饵受体）阻断OGL形成，并阻止sODF诱导的融合前破骨细胞的存活、多核化和陷窝形成活性。这些结果表明，ODF不仅调节破骨细胞的分化，而且通过受体RANK破骨细胞的功能。少

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