Epinephrine accelerates osteoblastic differentiation by enhancing bone morphogenetic protein signaling through a cAMP/protein kinase A signaling pathway.
Epinephrine accelerates osteoblastic differentiation by enhancing bone morphogenetic protein signaling through a cAMP/protein kinase A signaling pathway.
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肾上腺素通过 cAMP/蛋白激酶 A 信号通路增强骨形态发生蛋白信号传导，从而加速成骨细胞分化。
DOI：
10.1016/j.bone.2010.07.008
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发表时间：
2010
期刊：
影响因子：
4.1
通讯作者：
K. Takaoka
中科院分区：
文献类型：
--
作者：
T. Uemura;Y. Ohta;Yoshihiro Nakao;Tomoya Manaka;Hiroaki Nakamura;K. Takaoka
在体内和体外实验系统中，研究了局部使用一种儿茶酚胺对骨形态发生蛋白（BMP）诱导的异位骨形成的影响。肾上腺素增强BMP-2的骨诱导作用。因此，通过向可生物降解的BMP-2载体中添加低剂量（10、20、40或80μg）肾上腺素，BMP-2（5μg）异位诱导的听小骨质量以剂量依赖性方式增加。为了研究肾上腺素增强BMP活性的机制，使用成骨细胞进行了体外实验。细胞中碱性磷酸酶（ALP）的表达水平，成骨细胞分化的标志物，在BMP-2（50 ng/ml）的作用下持续升高，并在肾上腺素（10− 8 M）的作用下进一步升高。肾上腺素增强的ALP升高可被β2-肾上腺素能受体拮抗剂（Butoxamine）和蛋白激酶A抑制剂（H89）特异性消除。此外，BMP诱导的ALP和骨钙素（成骨细胞分化的标志蛋白）以及Osterix（终末分化为成骨细胞所必需的转录因子）在ST 2细胞中的mRNA表达通过加入肾上腺素（10− 8 M）显著增强。在使用Id 1基因（BMP的立即早期反应基因）的启动子序列的荧光素酶表达测定中，BMP-2处理（50 ng/ml）提高了荧光素酶活性，并通过添加肾上腺素（10− 8 M）进一步增强了该活性。肾上腺素增强的荧光素酶活性被废除的突变cAMP反应元件（CRE）序列中的Id 1启动子，表明CRE-binding转录蛋白诱导肾上腺素除了可能作为Smad介导的BMP信号增强。
Topical effects of a catecholamine on bone morphogenetic protein (BMP)-induced ectopic bone formation were investigated in both in vivo and in vitro experimental systems. Epinephrine enhanced bone induction by BMP-2. Thus, the mass of ossicles ectopically induced by BMP-2 (5μg) was increased by the addition of a low dose (10, 20, 40, or 80μg) of epinephrine into a biodegradable BMP-2 carrier, in a dose-dependent manner. To investigate the mechanism by which epinephrine enhances BMP activity, in vitro experiments were carried out using osteogenic cells. The expression level of alkaline phosphatase (ALP) in cells, a marker of osteoblastic differentiation, was consistently elevated by BMP-2 (50ng/ml) and was further elevated by the addition of epinephrine (10−8M). The epinephrine-enhanced ALP elevation was specifically abolished by an antagonist to β2-adrenergic receptors (Butoxamine) and by a protein kinase A inhibitor (H89). Furthermore, BMP-induced mRNA expression of ALP and osteocalcin (marker proteins of osteoblastic differentiation) and of Osterix (a transcription factor essential for terminal differentiation to osteoblasts) in ST2 cells was significantly enhanced by the addition of epinephrine (10−8M). In luciferase expression assays using the promoter sequence of the Id1 gene (an immediate early response gene to BMP), luciferase activity was elevated by BMP-2 treatment (50ng/ml) and this activity was further enhanced by the addition of epinephrine (10−8M). Epinephrine-enhanced luciferase activity was abolished by mutation of the cAMP-response element (CRE) sequence in the Id1 promoter, indicating that CRE-binding transcription proteins induced by epinephrine addition may act as enhancers of Smad-mediated BMP signaling.
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缺乏β-肾上腺素能受体的小鼠骨量增加，但无法免受卵巢切除术对骨骼的有害影响
影响因子：
4.8
作者：
Bouxsein, M. L.;Devlin, M. J.;Ferrari, S. L.
通讯作者：
Ferrari, S. L.
DOI：
10.1016/s0169-6009(08)80105-5
发表时间：
1993-12-01
期刊：
BONE AND MINERAL
影响因子：
--
作者：
MOORE, RE;SMITH, CK;TASHJIAN, AH
通讯作者：
TASHJIAN, AH
多巴胺能刺激培养的大鼠系膜细胞中 cAMP 的积累。
DOI：
10.1152/ajpheart.1987.253.2.h358
发表时间：
1987
期刊：
The American journal of physiology
影响因子：
--
作者：
Shultz,PJ;Sedor,JR;Abboud,HE
通讯作者：
Abboud,HE
影响因子：
4.1
作者：
Lecka-Czernik, Beata
通讯作者：
Lecka-Czernik, Beata