1,25-Dihydroxy vitamin D3 inhibits adipocyte differentiation and gene expression in murine bone marrow stromal cell clones and primary cultures.
1,25-Dihydroxy vitamin D3 inhibits adipocyte differentiation and gene expression in murine bone marrow stromal cell clones and primary cultures.
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DOI：
10.1210/endo.139.5.5970
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发表时间：
1998-05
期刊：
影响因子：
4.8
通讯作者：
K. Kelly;K. Kelly;J. Gimble;J. Gimble
中科院分区：
文献类型：
--
作者：
K. Kelly;K. Kelly;J. Gimble;J. Gimble
骨髓基质干细胞分化为脂肪细胞和成骨细胞。这两个谱系被认为是成骨细胞相关的，部分原因是观察到成骨细胞诱导因子1，25二羟基维生素D3 [1，25（OH）2D 3]抑制大鼠股骨来源的基质细胞培养物的脂肪形成。然而，关于这种类固醇激素的成脂作用的文献存在分歧。本研究采用两种不同类型的核激素受体（糖皮质激素受体（氢化可的松）或过氧化物酶体增殖物激活受体（噻唑烷二酮类））检测了1，25（OH）2D 3（10（-12）-10（-8）M）对小鼠股骨来源的骨髓基质细胞分化的影响。实验使用多能小鼠骨髓基质细胞系BMS 2及其亚克隆，以及原代衍生的小鼠骨髓基质细胞培养物。在所有系统检查，1，25（OH）2D 3阻断诱导的氢化可的松，甲基异丁基黄嘌呤，吲哚美辛的基础上，流式细胞术分析的脂质积累的脂肪形成。这与晚期脂肪细胞基因标记物aP 2和adipsin的信使RNA水平降低有关。在BMS 2亚克隆编号24中，1，25（OH）2D 3的作用具有浓度依赖性。而1，25（OH）2D 3部分抑制噻唑烷二酮诱导的脂肪形成的亲本BMS 2细胞系，它对噻唑烷二酮诱导的分化的BMS 2亚克隆和原代培养物的影响最小。这些发现表明，纳摩尔浓度的1，25（OH）2D 3完全抑制小鼠骨髓基质细胞对糖皮质激素类成脂激动剂的分化，但在用噻唑烷二酮诱导后，它是一种不太有效的成脂拮抗剂。这项工作支持1，25（OH）2D 3抑制小鼠股骨来源的骨髓基质细胞脂肪生成的结论。
Bone marrow stromal stem cells differentiate into adipocytes and osteoblasts. These two lineages are thought to be reciprocally related, in part due to the observation that the osteoblast-inducing factor, 1,25 dihydroxy vitamin D3 [1,25(OH)2D3], inhibited adipogenesis of rat femoral-derived stromal cell cultures. However, the literature is divided concerning the adipogenic effects of this steroid hormone. This work examined the effect of 1,25(OH)2D3 (10(-12)-10(-8) M) on murine femoral-derived bone marrow stromal cell differentiation in response to adipogenic agonists employing two different classes of nuclear hormone receptors: the glucocorticoid receptor (hydrocortisone) or peroxisome proliferator-activated receptors (thiazolidinediones). Experiments used the multipotent murine bone marrow stromal cell line, BMS2, and its subclones, as well as primary-derived murine bone marrow stromal cell cultures. In all systems examined, 1,25(OH)2D3 blocked adipogenesis induced by hydrocortisone, methylisobutylxanthine, and indomethacin based on flow cytometric analysis of lipid accumulation. This correlated with reduced messenger RNA levels of the late adipocyte gene markers, aP2 and adipsin. In the BMS2 subclone no. 24, the 1,25(OH)2D3 actions were concentration dependent. Whereas 1,25(OH)2D3 partially inhibited thiazolidinedione-induced adipogenesis in the parental BMS2 cell line, it had minimal effect on the thiazolidinedione-induced differentiation of the BMS2 subclone and primary cultures. These findings indicate that 1,25(OH)2D3, at nanomolar concentrations, completely inhibits murine bone marrow stromal cell differentiation in response to glucocorticoid-based adipogenic agonists but is a less effective adipogenic antagonist following induction with thiazolidinediones. This work supports the conclusion that 1,25(OH)2D3 inhibits murine femoral-derived bone marrow stromal cell adipogenesis.