Apelin suppresses apoptosis of human osteoblasts
Apelin suppresses apoptosis of human osteoblasts
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DOI：
10.1007/s10495-006-0489-7
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发表时间：
2007-01-01
期刊：
影响因子：
7.2
通讯作者：
Liao, Er-Yuan
中科院分区：
文献类型：
--
作者：
Xie, Hui;Yuan, Ling-Qing;Liao, Er-Yuan
目的：Apelin是最近发现的一种肽，是孤儿G蛋白偶联受体APJ的内源性配体。脂肪细胞可以表达和分泌apelin。成骨细胞表达apelin和APJ。本研究旨在探讨apelin对人成骨细胞凋亡的影响。结果：Apelin抑制血清剥夺诱导的人成骨细胞凋亡。用小干扰RNA（siRNA）抑制APJ消除了爱帕琳的抗凋亡活性。我们的研究还表明，在apelin处理下，Bcl-2蛋白表达增加，Bax蛋白表达减少。Apelin降低人成骨细胞中细胞色素c的释放和caspase-3的活化。Apelin激活磷脂酰肌醇-3激酶（PI-3激酶）和Akt。Apelin诱导的Akt活化可通过siRNA抑制APJ来阻断。LY 294002（PI-3激酶抑制剂）或1 L-6-羟甲基-手性-肌醇2-（R）-2-O-甲基-3-O-十八烷基碳酸酯（HIMO; Akt抑制剂）消除爱帕琳诱导的Akt活化，并且LY 294002或HIMO消除爱帕琳的抗凋亡活性。此外，爱帕琳还能防止糖皮质激素地塞米松诱导的细胞凋亡。结论：Apelin抑制血清缺乏诱导的人成骨细胞凋亡，并且抗凋亡作用是通过APJ/PI-3激酶/Akt信号通路介导的。
Objectives: Apelin is a recently discovered peptide that is the endogenous ligand for the orphan G-protein-coupled receptor APJ. Adipocytes can express and secrete apelin. Osteoblast can express apelin and APJ. The aim of this study was to investigate the action of apelin on apoptosis of human osteoblasts. Results: Apelin inhibited human osteoblasts apoptosis induced by serum deprivation. Suppression of APJ with small-interfering RNA (siRNA) abolished the anti-apoptotic activity of apelin. Our study also showed an increased Bcl-2 protein expression and decreased Bax protein expression under the treatment of apelin. Apelin decreased cytochrome c release and caspase-3 activation in human osteoblasts. Apelin activated phosphatidylinositol-3 kinase (PI-3 kinase) and Akt. The apelin-induced activation of Akt was blocked by suppression of APJ with siRNA. LY294002 (a PI-3 kinase inhibitor) or 1L-6-hydroxymethyl-chiro-inositol 2-(R)-2-O-methyl-3-O-octadecylcarbonate (HIMO; an Akt inhibitor) abolished apelin induced activation of Akt, and, LY294002 or HIMO abolished the anti-apoptotic activity of apelin. Furthermore, apelin protects against apoptosis induced by the glucocorticoid dexamethasone. Conclusions: Apelin suppresses serum deprivation-induced apoptosis of human osteoblasts and the anti-apoptotic action is mediated via the APJ/PI-3 kinase/Akt signaling pathway.