부산대학교 도서관

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.bcp.2007.04.020 Byline: Naibedya Chattopadhyay, Stephen J. Quinn, Olga Kifor, Chianping Ye, Edward M. Brown Keywords: Inositol phosphates; Cytosolic calcium; Non-selective cation channel; c-fos; Egr-1 HEK293 cells Abstract: 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 Sr.sup.2+ 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 Ca.sub.o.sup.2+ or Sr.sup.2+ concentration-dependently activated the CaR in HEK-CaR but not in non-transfected cells, but the potency of Sr.sup.2+ varied depending on the biological response tested. Sr.sup.2+ was less potent than Ca.sub.o.sup.2+ in stimulating inositol phosphate accumulation and in increasing Ca.sub.i.sup.2+, but was comparable to Ca.sub.o.sup.2+ in stimulating ERK phosphorylation and a non-selective cation channel, suggesting that Ca.sup.2+ and Sr.sup.2+ have differential effects on specific cellular processes. With physiological concentrations of Ca.sub.o.sup.2+, Sr.sup.2+-induced further CaR activation. Neither Sr.sup.2+ nor Ca.sub.o.sup.2+ affected the four parameters just described in non-transfected cells. In POB, Sr.sup.2+ stimulated cellular proliferation. This effect was CaR-mediated, as transfecting the cells with a dominant negative bovine CaR significantly attenuated Ca.sub.o.sup.2+-stimulated POB proliferation. Finally, Sr.sup.2+ significantly 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, Sr.sup.2+ is a full CaR agonist in HEK-CaR and POB, and, therefore, the anabolic effect of Sr.sup.2+ on bone in vivo could be mediated, in part, by the CaR. Author Affiliation: Division of Endocrinology, Diabetes and Hypertension and Membrane Biology Program, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, United States Article History: Received 17 February 2007; Accepted 24 April 2007