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Endocrine
Published in: Endocrine 3/2018

01-06-2018 | Original Article

The effects of Exendin-4 on bone marrow-derived mesenchymal cells

Authors: Paola Luciani, Benedetta Fibbi, Benedetta Mazzanti, Cristiana Deledda, Lara Ballerini, Alessandra Aldinucci, Susanna Benvenuti, Riccardo Saccardi, Alessandro Peri

Published in: Endocrine | Issue 3/2018

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Abstract

Purpose

GLP-1 receptor agonists are antidiabetic drugs currently used in the therapy of type 2 diabetes. Despite several in vitro and in vivo animal studies suggesting a beneficial effect of GLP-1 analogues on bone, in humans their skeletal effects are not clear and clinical studies report conflicting results.

Methods

We differentiated human mesenchymal stromal cells (hMSC) toward the adipogenic and the osteoblastic lineages, analysing the effect of Exendin-4 (EXE) before, during and after specific differentiations.

Results

We showed EXE ability to act selectively on a sub-population of hMSC characterised by a more stem potential, shifting them from G1 to S/M phase of cell cycle. We observed that EXE pre-treatment promotes both adipogenic and osteoblastic differentiations, possibly determined by an increased number of uncommitted progenitors. In fully differentiated cells, EXE affects mature adipocytes by increasing lipolysis, otherwise not altering osteoblasts metabolic activity. Moreover, the increased expression of osteoprotegerin, a modulator of the RANK/RANKL system, observed during osteogenic induction in presence of EXE, could negatively modulate osteoclastogenesis.

Conclusions

Our data suggest a complex action of EXE on bone, targeting the proliferation of mesenchymal progenitors, the metabolism of mature adipocytes and the modulation of osteoclastogenesis. Thus, an overall positive effect of this molecule on bone quality might be hypothesised.
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Metadata
Title
The effects of Exendin-4 on bone marrow-derived mesenchymal cells
Authors
Paola Luciani
Benedetta Fibbi
Benedetta Mazzanti
Cristiana Deledda
Lara Ballerini
Alessandra Aldinucci
Susanna Benvenuti
Riccardo Saccardi
Alessandro Peri
Publication date
01-06-2018
Publisher
Springer US
Published in
Endocrine / Issue 3/2018
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-017-1430-2

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