Liraglutide attenuates the osteoblastic differentiation of MC3T3‑E1 cells by modulating AMPK/mTOR signaling

Hu,Xiong‑Ke; Yin,Xin‑Hua; Zhang,Hong‑Qi; Guo,Chao‑Feng; Tang,Ming‑Xing

doi:10.3892/mmr.2016.5729

Liraglutide attenuates the osteoblastic differentiation of MC3T3‑E1 cells by modulating AMPK/mTOR signaling

Authors:
- Xiong‑Ke Hu
- Xin‑Hua Yin
- Hong‑Qi Zhang
- Chao‑Feng Guo
- Ming‑Xing Tang
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Affiliations: Department of Spine Surgery, Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China
Published online on: September 6, 2016 https://doi.org/10.3892/mmr.2016.5729
Pages: 3662-3668
Copyright: © Hu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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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