The calcium-sensing receptor (CaR) is involved in strontium ranelate-induced osteoblast proliferation
The calcium-sensing receptor (CaR) is involved in strontium ranelate-induced osteoblast proliferation
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DOI：
10.1016/j.bcp.2007.04.020
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发表时间：
2007-08-01
影响因子：
5.8
通讯作者：
Brown, Edward M.
中科院分区：
文献类型：
--
作者：
Chattopadhyay, Naibedya;Quinn, Stephen J.;Brown, Edward M.
兰氏锶对骨骼有几种有益的作用，并降低了绝经后骨质疏松症女性椎骨和髋部骨折的风险。我们研究了SR2+在HEK293细胞中是否通过细胞表面钙敏感受体（CAR）作用，可稳定地用牛汽车（HEK-CAR）和大鼠原代成骨细胞（POBS）稳定转染，内源性地表达汽车。抬高CO-0（2+）或SR2+浓度依赖性地激活了HEK-CAR中的汽车，但在非转染的细胞中却没有激活，而SR2+的效力则取决于测试的生物学反应。 SR2+在刺激肌醇磷酸盐积累和增加Ca-I（2+）中的效力不如CA-O（2+），但在刺激ERK磷酸化和非选择性阳离子通道中与CA-O（2+）相当，表明Ca2+和SR2+对特定细胞过程具有不同的影响。 SR2+诱导的进一步的CA-O（2+）生理浓度。 SR2+和CA-O（2+）均未影响未转染的细胞中刚刚描述的四个参数。在POB中，SR2+刺激了细胞增殖。该作用是CAR介导的，因为用显性牛的显着牛CA-O（2+）刺激的POB增殖将细胞转染。最后，SR2+ SI综合增加了与POB增殖有关的早期基因，C-FOS和EGR-1的mRNA水平，并通过过表达优势负面汽车来减弱这种效果。总之，SR2+是HEK-CAR和POB中的一种完整的汽车激动剂，因此，SR2+对体内骨骼的合成代谢作用可以部分由汽车介导。 （C）2007年由Elsevier Inc.出版
Strontium ranelate has several beneficial effects on bone and reduces the risk of vertebral and hip fractures in women with postmenopausal osteoporosis. We investigated whether Sr2+ acts via a cell surface calcium-sensing receptor (CaR) in HEK293 cells stably transfected with the bovine CaR (HEK-CaR) and rat primary osteoblasts (POBs) expressing the CaR endogenously. Elevating Co-0(2+) or Sr2+ concentration-dependently activated the CaR in HEK-CaR but not in non-transfected cells, but the potency of Sr2+, varied depending on the biological response tested. Sr2+ was less potent than Ca-o(2+) in stimulating inositol phosphate accumulation and in increasing Ca-i(2+), but was comparable to Ca-o(2+) in stimulating ERK phosphorylation and a non-selective cation channel, suggesting that Ca2+ and Sr2+ have differential effects on specific cellular processes. With physiological concentrations of Ca-o(2+), Sr2+-induced further CaR activation. Neither Sr2+ nor Ca-o(2+) affected the four parameters just described in non-transfected cells. In POB, Sr2+ stimulated cellular proliferation. This effect was CaR-mediated, as transfecting the cells with a dominant negative bovine CaR significantly attenuated Ca-o(2+)-stimulated POB proliferation. Finally, Sr2+ Si gnificantly increased the mRNA levels of the immediate early genes, c-fos and egr-1, which are involved in POB proliferation, and this effect was attenuated by overexpressing the dominant negative CaR. In conclusion, Sr2+ is a full CaR agonist in HEK-CaR and POB, and, therefore, the anabolic effect of Sr2+ on bone in vivo could be mediated, in part, by the CaR. (c) 2007 Published by Elsevier Inc.