Paola Luciani1, Benedetta Fibbi1, Benedetta Mazzanti2, Cristiana Deledda1, Lara Ballerini2, Alessandra Aldinucci3, Susanna Benvenuti1, Riccardo Saccardi2, Alessandro Peri4. 1. Endocrine Unit, Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy. 2. Haematology Unit, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy. 3. Department of NEUROFARBA, University of Florence, Florence, Italy. 4. Endocrine Unit, Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy. alessandro.peri@unifi.it.
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.
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.
Entities:
Keywords:
Bone marrow; Bone quality; Diabetes; GLP-1 agonists
Authors: S Benvenuti; I Cellai; P Luciani; C Deledda; S Baglioni; C Giuliani; R Saccardi; B Mazzanti; S Dal Pozzo; E Mannucci; A Peri; M Serio Journal: J Endocrinol Invest Date: 2007-10 Impact factor: 4.256
Authors: Bernardo Nuche-Berenguer; Paola Moreno; Pedro Esbrit; Sonia Dapía; José R Caeiro; Jesús Cancelas; Juan J Haro-Mora; María L Villanueva-Peñacarrillo Journal: Calcif Tissue Int Date: 2009-02-15 Impact factor: 4.333