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甲基磺酰甲烷增强间充质干细胞中骨形态发生蛋白-2诱导的成骨细胞分化。

Methylsulfonylmethane enhances BMP‑2‑induced osteoblast differentiation in mesenchymal stem cells.

作者信息

Kim Don Nam, Joung Youn Hee, Darvin Pramod, Kang Dong Young, Sp Nipin, Byun Hyo Joo, Cho Kwang Hyun, Park Kyung Do, Lee Hak Kyo, Yang Young Mok

机构信息

Department of Pathology, School of Medicine, Institute of Biomedical Science and Technology, Glocal Campus, Konkuk University, Seoul 143‑701, Republic of Korea.

National Institute of Animal Science, RDA, Cheonan 331‑801, Republic of Korea.

出版信息

Mol Med Rep. 2016 Jul;14(1):460-6. doi: 10.3892/mmr.2016.5274. Epub 2016 May 13.

Abstract

As human lifespans have increased, the incidence of osteoporosis has also increased. Methylsulfonylmethane (MSM) affects the process of mesenchymal stem cell (MSC) differentiation into osteoblasts via the Janus kinase 2 (Jak2)/signal transducer and activator of transcription (STAT)5b signaling pathway, and bone morphogenetic protein 2 (BMP‑2) is also known to significantly affect bone health. In addition, the phosphorylation of small mothers against decapentaplegic (Smad)1/5/8 regulates the Runt‑related transcription factor 2 (Runx2) gene, which encodes a transcription factor for osteoblast differentiation markers. In the present study, the differentiation of MSCs treated with MSM, BMP‑2, and their combination were examined. The differentiation of osteoblasts was demonstrated through observation of morphological changes and mineralization, using alizarin red and Von Kossa staining. Western blotting analysis demonstrated that the combination of MSM and BMP-2 increased the phosphorylation of the BMP signaling-associated protein, Smad1/5/8. Combination of MSM and BMP-2 significantly increased osteogenic differentiation and mineralization of the MSCs compared with either MSM or BMP-2 alone. Additionally, reverse transcription-polymerase chain reaction analysis demonstrated that combination of MSM and BMP-2 increased the expression level of the Runx2 gene and the osteoblast differentiation marker genes, alkaline phosphatase, bone sialoprotein and osteocalcin, in MSCs compared with controls. Thus, the combination of MSM and BMP-2 may promote the differentiation of MSCs into osteoblasts.

摘要

随着人类寿命的延长,骨质疏松症的发病率也有所上升。甲基磺酰甲烷(MSM)通过Janus激酶2(Jak2)/信号转导子和转录激活子(STAT)5b信号通路影响间充质干细胞(MSC)向成骨细胞的分化过程,并且已知骨形态发生蛋白2(BMP-2)也会显著影响骨骼健康。此外,小分子抗五聚体蛋白(Smad)1/5/8的磷酸化调节Runx相关转录因子2(Runx2)基因,该基因编码成骨细胞分化标志物的转录因子。在本研究中,检测了用MSM、BMP-2及其组合处理的MSC的分化情况。通过使用茜素红和冯科萨染色观察形态变化和矿化来证明成骨细胞的分化。蛋白质免疫印迹分析表明,MSM和BMP-2的组合增加了BMP信号相关蛋白Smad1/5/8的磷酸化。与单独使用MSM或BMP-2相比,MSM和BMP-2的组合显著增加了MSC的成骨分化和矿化。此外,逆转录-聚合酶链反应分析表明,与对照组相比,MSM和BMP-2的组合增加了MSC中Runx2基因以及成骨细胞分化标志物基因碱性磷酸酶、骨唾液蛋白和骨钙素的表达水平。因此,MSM和BMP-2的组合可能促进MSC向成骨细胞的分化。

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