Liraglutide attenuates the osteoblastic differentiation of MC3T3‑E1 cells by modulating AMPK/mTOR signaling.
Liraglutide attenuates the osteoblastic differentiation of MC3T3‑E1 cells by modulating AMPK/mTOR signaling.
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利拉鲁肽通过调节 AMPK/mTOR 信号减弱 MC3T3-E1 细胞的成骨细胞分化
DOI：
10.3892/mmr.2016.5729
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发表时间：
2016-10
影响因子：
3.4
通讯作者：
Tang MX
中科院分区：
文献类型：
--
作者：
Hu XK;Yin XH;Zhang HQ;Guo CF;Tang MX
利拉鲁肽是胰高血糖素样肽-1的合成类似物，用于治疗2型糖尿病和肥胖症。利拉鲁肽先前已被证明可阻止人血管平滑肌细胞的成骨细胞分化，从而减缓动脉钙化，但其对骨形成的影响尚不清楚。本研究使用茜素红S染色研究了利拉鲁肽对成骨细胞分化的影响，并通过蛋白质印迹分析检查了调节作用的分子机制。本研究表明，磷酸化腺苷单磷酸活化蛋白激酶（p-AMPK）的蛋白表达水平在成骨分化培养基中的成骨分化过程中在MC 3 T3-E1细胞下调，而转化生长因子-β（TGF-β）和磷酸化哺乳动物雷帕霉素靶蛋白（p-mTOR）的蛋白表达水平增加。随后证明利拉鲁肽可剂量依赖性减弱MC 3 T3-E1细胞的成骨细胞分化，上调p-AMPK，下调p-mTOR和TGF-β蛋白表达水平。用AMPK特异性抑制剂化合物C治疗消除了利拉鲁肽对成骨细胞分化以及p-mTOR和TGF-β下调的影响。mTOR激活剂MHY 1485也消除了利拉鲁肽对成骨细胞分化的抑制作用，并导致p-mTOR和TGF-β下调，但未减弱利拉鲁肽诱导的p-AMPK蛋白表达水平升高。本研究的结果表明，利拉鲁肽通过调节AMPK/mTOR信号转导减弱MC 3 T3-E1细胞的成骨细胞分化。本研究揭示了利拉鲁肽的一种新功能，有助于了解其在临床环境中的药理学和生理学作用。
Liraglutide, a synthetic analogue of glucagon-like peptide-1, is utilized in the treatment of type 2 diabetes and obesity. Liraglutide has been previously demonstrated to prevent osteoblastic differentiation of human vascular smooth muscle cells, resulting in the slowing of arterial calcification, however, its effect on bone formation remains unclear. The present study investigated the effect of liraglutide on osteoblastic differentiation using Alizarin Red S staining, and examined the molecular mechanisms underlying the regulatory effect by western blot analysis. The present study demonstrated that protein expression levels of phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK) were downregulated in MC3T3-E1 cells during osteoblastic differentiation in commercial osteogenic differentiation medium, whereas protein expression levels of transforming growth factor-β (TGF-β) and phosphorylated mammalian target of rapamycin (p-mTOR) increased. Liraglutide was subsequently demonstrated to dose-dependently attenuate the osteoblastic differentiation of MC3T3-E1 cells, to upregulate p-AMPK, and downregulate p-mTOR and TGF-β protein expression levels. Treatment with an AMPK-specific inhibitor, Compound C, eradicated the effect of liraglutide on osteoblastic differentiation, and p-mTOR and TGF-β downregulation. An mTOR activator, MHY1485, also abolished the inhibitory effect of liraglutide on osteoblastic differentiation, and resulted in p-mTOR and TGF-β downregulation, but did not attenuate the liraglutide-induced increase in p-AMPK protein expression levels. The results of the present study demonstrate that liraglutide attenuates osteoblastic differentiation of MC3T3-E1 cells via modulation of AMPK/mTOR signaling. The present study revealed a novel function of liraglutide, which contributes to the understanding of its pharmacological and physiological effects in clinical settings.
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DOI：
10.4081/ejh.2013.e40
发表时间：
2013-12-04
期刊：
European journal of histochemistry : EJH
影响因子：
--
作者：
Latella G;Vetuschi A;Sferra R;Speca S;Gaudio E
通讯作者：
Gaudio E
DOI：
10.1083/jcb.96.1.191
发表时间：
1983-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Sudo H;Kodama HA;Amagai Y;Yamamoto S;Kasai S
通讯作者：
Kasai S
影响因子：
5.6
作者：
OWEN, TA;ARONOW, M;STEIN, GS
通讯作者：
STEIN, GS
脂联素通过 AMPK/mTOR 通路减弱血管平滑肌细胞的成骨分化
影响因子：
3.7
作者：
Zhan, Jun-Kun;Wang, Yan-Jiao;Liu, You-Shuo
通讯作者：
Liu, You-Shuo
影响因子：
5.8
作者：
Gough, S. C. L.
通讯作者：
Gough, S. C. L.