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硼酸对人脂肪来源干细胞(hADSCs)成肌分化的剂量依赖性效应

Dose-dependent Effect of Boric Acid on Myogenic Differentiation of Human Adipose-derived Stem Cells (hADSCs).

作者信息

Apdik Hüseyin, Doğan Ayşegül, Demirci Selami, Aydın Safa, Şahin Fikrettin

机构信息

Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University, 34755, Kayışdağı, Istanbul, Turkey.

出版信息

Biol Trace Elem Res. 2015 Jun;165(2):123-30. doi: 10.1007/s12011-015-0253-3. Epub 2015 Feb 1.

Abstract

Boron, a vital micronutrient for plant metabolism, is not fully elucidated for embryonic and adult body development, and tissue regeneration. Although optimized amount of boron supplement has been shown to be essential for normal gestational development in zebrafish and frog and beneficial for bone regeneration in higher animals, effects of boron on myogenesis and myo-regeneration remains to be solved. In the current study, we investigated dose-dependent activity of boric acid on myogenic differentiation of human adipose-derived stem cells (hADSCs) using immunocytochemical, gene, and protein expression analysis. The results revealed that while low- (81.9 μM) and high-dose (819.6 μM) boron treatment increased myogenic gene expression levels such as myosin heavy chain (MYH), MyoD, myogenin, and desmin at day 4 of differentiation, high-dose treatment decreased myogenic-related gene and protein levels at day 21 of differentiation, confirmed by immunocytochemical analysis. The findings of the study present not only an understanding of boron's effect on myogenic differentiation but also an opportunity for the development of scaffolds to be used in skeletal tissue engineering and supplements for embryonic muscle growth. However, fine dose tuning and treatment period arranging are highly warranted as boron treatment over required concentrations and time might result in detrimental outcomes to myogenesis and myo-regeneration.

摘要

硼是植物新陈代谢所必需的微量营养素,但其在胚胎和成年机体发育以及组织再生方面的作用尚未完全阐明。尽管已证明适量补充硼对斑马鱼和青蛙的正常妊娠发育至关重要,且对高等动物的骨骼再生有益,但硼对肌生成和肌再生的影响仍有待解决。在本研究中,我们使用免疫细胞化学、基因和蛋白质表达分析方法,研究了硼酸对人脂肪来源干细胞(hADSCs)肌源性分化的剂量依赖性活性。结果显示,在分化第4天,低剂量(81.9 μM)和高剂量(819.6 μM)硼处理可增加肌源性基因表达水平,如肌球蛋白重链(MYH)、肌分化抗原(MyoD)、肌细胞生成素和结蛋白;而在分化第21天,高剂量处理则降低了肌源性相关基因和蛋白质水平,免疫细胞化学分析证实了这一点。该研究结果不仅有助于了解硼对肌源性分化的影响,还为开发用于骨骼组织工程的支架以及促进胚胎肌肉生长的补充剂提供了契机。然而,由于硼在超过所需浓度和时间进行处理可能会对肌生成和肌再生产生有害影响,因此非常有必要对剂量进行精细调整并安排治疗时间。

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