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首页> 外文期刊>Cellular Physiology and Biochemistry >Rosuvastatin Promotes Osteoblast Differentiation and Regulates SLCO1A1 Transporter Gene Expression in MC3T3-E1 Cells
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Rosuvastatin Promotes Osteoblast Differentiation and Regulates SLCO1A1 Transporter Gene Expression in MC3T3-E1 Cells

机译：罗苏伐他汀促进成骨细胞分化并调节MC3T3-E1细胞中SLCO1A1转运蛋白基因的表达

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Rosuvastatin (RSV) is a synthetic statin with favourable pharmacologic properties including minimal metabolism, hepatic selectivity and enhanced inhibition of HMG-CoA reductase. An induction of osteoblast differentiation has been reported iin vitro/i with lipophilic statins but not with RSV, which, like pravastatin, is relatively hydrophilic compared with other statins. To mediate its action, an active transport mechanism via solute carrier (SLC) transporters from the SLC16, SLC21/SLCO and SLC22 gene family - specifically Slc16a1, Slco1a1, Slco2b1 and Slc22a8 - may be present to allow effective entry in osteoblastic cells. In this study, we demonstrate that RSV induced osteoblast differentiation, as measured by increased BMP-2 gene expression and secretion, and ALP activity in MC3T3-E1 osteoblast cells, without significantly affecting cell proliferation within the concentration range of 0.001-10 µM. Low concentrations of RSV (0.001-0.01 µM) were protective against cell death whereas higher concentrations (10-100 µM) showed cytotoxicity. Moreover, MC3T3-E1 osteoblasts expressed high levels of Slco1a1 and Slc16a1 mRNA and low levels of Slco2b1 and Slc22a8 mRNA, when compared with kidney and liver tissues from mice. Slco1a1 gene expression increased 12-fold during osteoblast differentiation and was further regulated after RSV treatment. In conclusion, as for other statins, RSV promotes osteoblast differentiation, and also, demonstrated for the first time, regulates the expression of Slco1a1, which may constitute the transport system for RSV across the cell membrane in mature osteoblasts.
机译：罗苏伐他汀（RSV）是一种合成的他汀类药物，具有良好的药理特性，包括最小的代谢，肝选择性和对HMG-CoA还原酶的抑制作用。据报道，亲脂性他汀类药物体外诱导成骨细胞分化，但与普伐他汀类似，RSV与其他他汀类药物相比具有亲水性，但没有RSV。为了介导其作用，可能存在经由来自SLC16，SLC21 / SLCO和SLC22基因家族的溶质载体（SLC）转运蛋白的主动转运机制，特别是Slc16a1，Slco1a1，Slco2b1和Slc22a8，以允许有效进入成骨细胞。在这项研究中，我们证明了RSV诱导的成骨细胞分化（通过增加BMP-2基因表达和分泌以及MC3T3-E1成骨细胞中的ALP活性来衡量）在0.001-10 µM的浓度范围内不会显着影响细胞增殖。低浓度的RSV（0.001-0.01 µM）可以防止细胞死亡，而较高的浓度（10-100 µM）则具有细胞毒性。此外，与小鼠的肾脏和肝脏组织相比，MC3T3-E1成骨细胞表达高水平的Slco1a1和Slc16a1 mRNA，低水平的Slco2b1和Slc22a8 mRNA。 Slco1a1基因表达在成骨细胞分化过程中增加了12倍，并在RSV治疗后进一步受到调节。总之，与其他他汀类药物一样，RSV促进成骨细胞分化，并且首次证明其调节Slco1a1的表达，这可能构成成熟成骨细胞中RSV跨细胞膜的转运系统。

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