CHARACTERIZATION OF BETA-ADRENERGIC RECEPTORS ON RAT AND HUMAN OSTEOBLAST-LIKE CELLS AND DEMONSTRATION THAT BETA-RECEPTOR AGONISTS CAN STIMULATE BONE-RESORPTION IN ORGAN-CULTURE
CHARACTERIZATION OF BETA-ADRENERGIC RECEPTORS ON RAT AND HUMAN OSTEOBLAST-LIKE CELLS AND DEMONSTRATION THAT BETA-RECEPTOR AGONISTS CAN STIMULATE BONE-RESORPTION IN ORGAN-CULTURE
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DOI：
10.1016/s0169-6009(08)80105-5
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发表时间：
1993-12-01
期刊：
影响因子：
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通讯作者：
TASHJIAN, AH
中科院分区：
文献类型：
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作者：
MOORE, RE;SMITH, CK;TASHJIAN, AH
我们通过受体结合分析表明，大鼠ROS 17/2.8成骨细胞样细胞上存在β-2肾上腺素能受体。这通过从mRNA复制的cDNA的PCR扩增证实。即使在PCR分析提供的灵敏度水平下，β-1肾上腺素受体亚型也不存在，并且其mRNA也无法检测到。ROS 17/2.8细胞上存在的β-肾上腺素能受体是功能性的，如通过配体诱导的cAMP产生的增强所测量的。我们研究了肾上腺素能受体激动剂是否可以模拟PTH的作用，以刺激新生小鼠颅骨器官培养的骨吸收。甲状旁腺素诱导cAMP大量增加，而去甲肾上腺素和异丙肾上腺素诱导一个小的，但显着的增加。在磷酸二酯酶抑制剂和抗氧化剂的存在下，去甲肾上腺素始终刺激骨吸收。为了确定功能性β-肾上腺素能受体是否是ROS 17/2.8细胞所特有的，还检查了人SaOS-2成骨细胞样细胞通过去甲肾上腺素对cAMP产生的增强，并且获得了基本相同的结果。因此，肾上腺素能激动剂有效地激活两种成骨细胞样细胞上的β受体，并可刺激完整小鼠颅骨中的骨吸收。
We have shown by receptor-binding analyses that the beta-2 adrenergic receptor is present on rat ROS 17/2.8 osteoblast-like cells. This was confirmed by PCR amplification of cDNA copied from the mRNA. The beta-1 adrenoreceptor subtype was absent and its mRNA was not detectable, even at the level of sensitivity afforded by PCR analysis. The beta-adrenergic receptors present on ROS 17/2.8 cells were functional as measured by ligand-induced enhancement of cAMP production. We investigated whether adrenergic agonists could mimic the action of PTH to stimulate bone resorption in neonatal mouse calvariae in organ culture. PTH induced a large increase in cAMP while norepinephrine and isoproterenol induced a small but significant increase. In the presence of a phosphodiesterase inhibitor and an antioxidant, norepinephrine consistently stimulated bone resorption. In order to determine whether functional beta-adrenergic receptors were unique to ROS 17/2.8 cells, human SaOS-2 osteoblast-like cells were also examined for enhancement of cAMP production by norepinephrine, and essentially the same results were obtained. Thus, adrenergic agonists efficiently activate beta-receptors on two osteoblast-like cells and can stimulate bone resorption in intact mouse calvariae.