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首页> 外文期刊>Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research >Alendronate has an anabolic effect on bone through the differentiation of mesenchymal stem cells.
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Alendronate has an anabolic effect on bone through the differentiation of mesenchymal stem cells.

机译：阿仑膦酸盐通过间充质干细胞的分化对骨骼具有合成代谢作用。

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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 x 10(5) cells/well in 100-cm2 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 PPARgamma2 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 PPARgamma2 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.
机译：我们致力于使MSC分化为成骨细胞或脂肪细胞，并研究了ALN对脂肪形成和成骨细胞的作用。 ALN抑制脂肪生成，同时促进成骨细胞的分化和活性。我们的结果揭示了ALN在分化骨髓细胞中的新的合成代谢作用。简介：阿仑膦酸盐（ALN）通过调节破骨细胞活性来预防绝经后患者的骨质流失。但是，它也已被证明在老年人中是有效的，因为老年人的病理生理机制是成脂作用超过成骨作用。这项研究的目的是确定ALN对成骨细胞和脂肪形成的体外作用。材料与方法：将人间充质干细胞（MSCs）以5 x 10（5）细胞/孔的密度接种在含有MSC生长培养基的100 cm2皿中。汇合后，细胞致力于分化，添加有或无1,25（OH）2D3（10（-8）M）的成脂或成骨培养基，并以浓度递增（10（-9）至10（-7）的ALN补充）M）。未处理的分化MSC用作对照。以一定的时间间隔（第1周和第2周）进行碱性磷酸酶（ALP），油红O和茜素红染色。另外，在蛋白质提取物中测量了成骨和脂肪形成转录因子的表达水平。最后，评估了ALN对PPARgamma2核激活复合物的影响。结果：我们发现ALN对成骨细胞具有显着且剂量依赖性的作用。在介质中存在1,25（OH）2D3并不能改善这种效果。此外，通过表型变化和脂质滴数量减少证实，向培养基中添加ALN和1,25（OH）2D3均会影响MSCs的成脂分化。最后，在用ALN或ALN + 1,25（OH）2D3处理的脂肪分化的MSC中，脂肪形成转录因子的表达和PPARgamma2激活减少。结论：本研究显示通过刺激MSC的成骨分化，ALN具有潜在的合成代谢作用。此外，还发现了先前未知的ALN对骨髓脂肪形成的抑制作用。

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