Alendronate Has an Anabolic Effect on Bone Through the Differentiation of Mesenchymal Stem Cells

Authors

  • Gustavo Duque,

    Corresponding author
    1. Division of Geriatric Medicine, Department of Medicine, McGill University, Montreal, Quebec, Canada
    2. Lady Davis Institute for Medical Research, McGill University, Montreal, Quebec, Canada
    • Address reprint requests to: Gustavo Duque, MD, PhD, Division of Geriatric Medicine, McGill University, 3755 Chemin de la Cote Sainte Catherine, Montreal, Quebec H3T 1E2, Canada
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  • Daniel Rivas

    1. Lady Davis Institute for Medical Research, McGill University, Montreal, Quebec, Canada
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  • Dr Duque serves as consultant to Procter and Gamble Pharmaceuticals and Merck-Frosst Canada. Dr Rivas states that he has no conflicts of interest.

  • Published online on July 2, 2007

Abstract

We committed MSCs to differentiate into either osteoblasts or adipocytes and examined the effect of ALN on both adipogenesis and osteoblastogenesis. ALN inhibited adipogenesis while promoting osteoblast differentiation and activity. Our results reveal a new anabolic effect of ALN in differentiating bone marrow cells.

Introduction: Alendronate (ALN) prevents bone loss in postmenopausal patients through the regulation of osteoclastic activity. However, it has also proven to be effective in older adults where the pathophysiological mechanism is the predominance of adipogenesis over osteoblastogenesis. The aim of this study is to determine the in vitro effect of ALN on both osteoblastogenesis and adipogenesis.

Materials and Methods: Human mesenchymal stem cells (MSCs) were plated at a density of 5 × 105 cells/well in 100-cm 2 dishes containing MSC growth media. After confluence, cells were committed to differentiate adding either adipogenic or osteogenic media with and without 1,25(OH)2D3 (10−8 M) and supplemented with ALN at increasing concentrations (10−9 to 10−7 M). Untreated differentiating MSCs were used as control. Alkaline phosphatase (ALP), oil red O, and Alizarin red staining were performed at timed intervals (weeks 1 and 2). Additionally, levels of expression of both osteogenesis and adipogenesis transcription factors were measured in protein extracts. Finally, the effect of ALN on PPARγ2 nuclear activation complex was assessed.

Results: We found that ALN has a significant and dose-dependent effect on osteoblastogenesis. This effect was not modified by the presence of 1,25(OH)2D3 in the medium. Furthermore, adipogenic differentiation of MSCs was affected by addition of both ALN and 1,25(OH)2D3 to the media as confirmed by phenotype changes and lower number of lipid droplets. Finally, expression of adipogenic transcription factors and PPARγ2 activation were reduced in adipose differentiating MSCs treated with either ALN or ALN + 1,25(OH)2D3.

Conclusions: This study shows a potential anabolic effect of ALN in vitro through the stimulation of osteogenic differentiation of MSCs. Additionally, a previously unknown inhibitory effect of ALN on bone marrow adipogenesis was also found.

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