Physiological changes in extracellular calcium concentration directly control osteoblast function in the absence of calciotropic hormones
Physiological changes in extracellular calcium concentration directly control osteoblast function in the absence of calciotropic hormones
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DOI：
10.1073/pnas.0306141101
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发表时间：
2004-04-06
影响因子：
11.1
通讯作者：
Riccardi, D
中科院分区：
文献类型：
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作者：
Dvorak, MM;Siddiqua, A;Riccardi, D
我们研究了细胞外游离钙离子浓度（[Ca2+]（o））变化对成骨细胞功能的直接影响以及钙敏感受体（CaR）介导这些反应的参与。在成骨细胞模型、新鲜分离的胎鼠颅骨细胞和小鼠克隆成骨细胞2T3细胞以及新鲜冷冻的人下颌骨和大鼠股骨未脱钙制剂中检测到CaR mRNA和蛋白。在胎鼠颅骨细胞中，升高[Ca 2 +]（o）和用钆（一种非渗透性CaR激动剂）处理，导致细胞外信号调节激酶1和2、Akt和糖原合成酶激酶3 β磷酸化，与细胞存活和增殖的信号一致。与此一致，在这些条件下细胞数量增加。成骨细胞分化标志物核心结合因子all、骨钙素、骨桥蛋白和胶原1 mRNA的表达因高[Ca2+]（o）而增加，矿化结节形成也是如此。[Ca 2 +]（o）在1.2至1.8 mM之间时碱性磷酸酶活性最大。NIPS 89636对CaR的抑制可阻断对CaR激动剂的反应。总之，我们表明，[Ca2+]（o）从生理值的小偏差有深远的影响骨细胞的命运，通过钙受体和独立的全身钙肽。
We investigated the direct effects of changes in free ionized extracellular calcium concentrations ([Ca2+](o)) on osteoblast function and the involvement of the calcium-sensing receptor (CaR) in mediating these responses. CaR mRNA and protein were detected in osteoblast models, freshly isolated fetal rat calvarial cells and murine clonal osteoblastic 2T3 cells, and in freshly frozen, undecalcified preparations of human mandible and rat femur. In fetal rat calvarial cells, elevating [Ca2+](o) and treatment with gadolinium, a nonpermeant CaR agonist, resulted in phosphorylation of the extracellular signal-regulated kinases 1 and 2, Akt, and glycogen-synthase kinase 3beta, consistent with signals of cell survival and proliferation. In agreement, cell number was increased under these conditions. Expression of the osteoblast differentiation markers core binding factor all, osteocalcin, osteopontin, and collagen 1 mRNAs was increased by high [Ca2+](o), as was mineralized nodule formation. Alkaline phosphatase activity was maximal for [Ca2+](o) between 1.2 and 1.8 mM. inhibition of CaR by NIPS 89636 blocked responses to the CaR agonists. In conclusion, we show that small deviations of [Ca2+](o) from physiological values have a profound impact on bone cell fate, by means of the CaR and independently of systemic calciotropic peptides.