Metabolic acidosis increases intracellular calcium in bone cells through activation of the proton receptor OGR1.
Metabolic acidosis increases intracellular calcium in bone cells through activation of the proton receptor OGR1.
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DOI：
10.1359/jbmr.081015
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发表时间：
2009-02
期刊：
影响因子：
--
通讯作者：
Bushinsky DA
中科院分区：
文献类型：
--
作者：
Frick KK;Krieger NS;Nehrke K;Bushinsky DA
代谢性酸中毒增加尿钙而不增加肠道吸收，导致骨钙丢失。目前尚不清楚骨细胞如何检测质子浓度的增加。为了确定哪些G蛋白偶联质子敏感受体在骨中表达，进行PCR，并检测OGR 1、TDAG 8、G2A和GPR 4的产物。我们测试的假设，G蛋白偶联的质子传感器，OGR 1，是一个H+敏感受体在骨。为了确定酸诱导的骨吸收是否涉及OGR 1，我们在中性pH（NTL）或酸性（MET）培养基± OGR 1抑制剂CuCl 2中孵育小鼠颅骨。CuCl 2可降低MET诱导的Ca流出。我们使用灌注骨细胞的荧光成像来确定MET是否增加Cai。MET灌注诱导单个骨细胞中Cai的快速、非流动性增加。为了确定OGR 1转染到异源细胞类型中是否会增加Cai对H+的反应，我们灌注了用小鼠OGR 1 cDNA转染的中国仓鼠卵巢（CHO）细胞。MET灌注诱导OGR 1转染的CHO细胞中Cai快速增加。这些数据表明，OGR 1诱导Cai增加，以响应MET，是成骨细胞质子传感器的主要候选者。
Metabolic acidosis increases urine Ca without increasing intestinal absorption, leading to bone Ca loss. It is unclear how bone cells detect the increase in proton concentration. To determine which G protein-coupled proton sensing receptors are expressed in bone, PCR was performed, and products were detected for OGR1, TDAG8, G2A, and GPR4. We tested the hypothesis that the G protein-coupled proton sensor, OGR1, is an H+-sensing receptor in bone. To determine whether acid-induced bone resorption involves OGR1, we incubated mouse calvariae in neutral pH (NTL) or acidic (MET) medium ± the OGR1 inhibitor CuCl2. CuCl2 decreased MET-induced Ca efflux. We used fluorescent imaging of perfused bone cells to determine whether MET increases Cai. Perfusion with MET induced a rapid, flow-independent, increase in Cai in individual bone cells. To determine whether transfection of OGR1 into a heterologous cell type would increase Cai in response to H+, we perfused Chinese hamster ovary (CHO) cells transfected with mouse OGR1 cDNA. Perfusion with MET induced a rapid increase in Cai in OGR1-transfected CHO cells. These data indicate that OGR1 induces an increase in Cai in response to MET and is a prime candidate for an osteoblast proton sensor.
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影响因子：
--
作者：
KRIEGER, NS;SESSLER, NE;BUSHINSKY, DA
通讯作者：
BUSHINSKY, DA
DOI：
10.1016/j.bbrc.2005.09.054
发表时间：
2005-11-11
影响因子：
3.1
作者：
Jahr, H;van Driel, M;van Leeuwen, JPTM
通讯作者：
van Leeuwen, JPTM
影响因子：
--
作者：
BUSHINSKY, DA
通讯作者：
BUSHINSKY, DA
影响因子：
6.2
作者：
Kamioka, Hiroshi;Sugawara, Yasuyo;Takano-Yamamoto, Teruko
通讯作者：
Takano-Yamamoto, Teruko
影响因子：
13.6
作者：
Jehle, Sigrid;Zanetti, Antonella;Krapf, Reto
通讯作者：
Krapf, Reto