MSM enhances GH signaling via the Jak2/STAT5b pathway in osteoblast-like cells and osteoblast differentiation through the activation of STAT5b in MSCs.
MSM enhances GH signaling via the Jak2/STAT5b pathway in osteoblast-like cells and osteoblast differentiation through the activation of STAT5b in MSCs.
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DOI：
10.1371/journal.pone.0047477
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Yang YM
中科院分区：
文献类型：
--
作者：
Joung YH;Lim EJ;Darvin P;Chung SC;Jang JW;Do Park K;Lee HK;Kim HS;Park T;Yang YM
甲基磺酰甲烷（MSM）是一种天然存在的硫化合物，具有众所周知的抗氧化特性和抗炎活性。但是，它对骨骼的影响是未知的。生长激素（GH）是骨生长和骨代谢的调节因子。GH激活几种信号通路，如Janus激酶（Jak）/信号转导和转录激活因子（STAT）通路，从而调节包括胰岛素样生长因子（IGF）-1在内的基因的表达。GH直接和通过IGF-1发挥作用，IGF-1通过激活IGF-1受体（IGF-1 R）发出信号。本研究旨在探讨MSM对成骨细胞内Jak/STAT信号通路GH信号通路的影响及对原代骨髓间充质干细胞（MSCs）分化的影响。MSM对成骨细胞和MSCs无毒性作用。MSM可增加成骨细胞和MSCs中IGF-1 R、p-IGF-1 R、STAT 5 b、p-STAT 5 b和Jak 2等GH相关蛋白的表达。MSM可增加成骨细胞IGF-1 R和GHR mRNA的表达。Jak 2激酶抑制剂AG 490可抑制MSM诱导的IGF-1 R和GHR的表达。MSM诱导STAT 5与IGF-1 R结合，并增加IGF-1和IGF-1 R启动子活性。通过免疫沉淀和Western印迹分析细胞提取物表明，MSM增强GH诱导的Jak 2/STAT 5 b活化。我们发现MSM和GH，单独或联合，激活GH信号通过Jak 2/STAT 5 b途径在UMR-106细胞。利用siRNA分析，我们发现STAT 5 b在C3 H10 T1/2细胞中GH信号激活中起重要作用。成骨标志物基因（ALP、ON、OCN、BSP、OSX和Runx 2）被MSM激活，并且siRNA介导的STAT 5 b敲低抑制MSM诱导的成骨标志物表达。MSM还能提高骨髓间充质干细胞的碱性磷酸酶活性和矿化能力。综上所述，这些结果表明MSM可以通过激活STAT 5 b促进MSC的成骨分化。
Methylsulfonylmethane (MSM) is a naturally occurring sulfur compound with well-known anti-oxidant properties and anti-inflammatory activities. But, its effects on bone are unknown. Growth hormone (GH) is regulator of bone growth and bone metabolism. GH activates several signaling pathways such as the Janus kinase (Jak)/signal transducers and activators of transcription (STAT) pathway, thereby regulating expression of genes including insulin-like growth factor (IGF)-1. GH exerts effects both directly and via IGF-1, which signals by activating the IGF-1 receptor (IGF-1R). In this study, we investigated the effects of MSM on the GH signaling via the Jak/STAT pathway in osteoblasts and the differentiation of primary bone marrow mesenchymal stem cells (MSCs). MSM was not toxic to osteoblastic cells and MSCs. MSM increased the expression of GH-related proteins including IGF-1R, p-IGF-1R, STAT5b, p-STAT5b, and Jak2 in osteoblastic cells and MSCs. MSM increased IGF-1R and GHR mRNA expression in osteoblastic cells. The expression of MSM-induced IGF-1R and GHR was inhibited by AG490, a Jak2 kinase inhibitor. MSM induced binding of STAT5 to the IGF-1R and increased IGF-1 and IGF-1R promoter activities. Analysis of cell extracts by immunoprecipitation and Western blot showed that MSM enhanced GH-induced activation of Jak2/STAT5b. We found that MSM and GH, separately or in combination, activated GH signaling via the Jak2/STAT5b pathway in UMR-106 cells. Using siRNA analysis, we found that STAT5b plays an essential role in GH signaling activation in C3H10T1/2 cells. Osteogenic marker genes (ALP, ON, OCN, BSP, OSX, and Runx2) were activated by MSM, and siRNA-mediated STAT5b knockdown inhibited MSM-induced expression of osteogenic markers. Furthermore, MSM increased ALP activity and the mineralization of MSCs. Taken together, these results indicated that MSM can promote osteogenic differentiation of MSCs through activation of STAT5b.
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影响因子：
3.7
作者：
Lim EJ;Hong DY;Park JH;Joung YH;Darvin P;Kim SY;Na YM;Hwang TS;Ye SK;Moon ES;Cho BW;Do Park K;Lee HK;Park T;Yang YM
通讯作者：
Yang YM
影响因子：
5.2
作者：
Joung, Youn-Hee;Lim, Eun-Joung;Yang, Young Mok
通讯作者：
Yang, Young Mok
影响因子：
158.5
作者：
Kofoed, EM;Hwa, V;Rosenfeld, RG
通讯作者：
Rosenfeld, RG
DOI：
10.1016/j.bbrc.2007.04.201
发表时间：
2007-07-06
影响因子：
3.1
作者：
Joung, Youn-Hee;Lee, Moon-Young;Yang, Young Mok
通讯作者：
Yang, Young Mok
影响因子：
4.2
作者：
KASSEM, M;BLUM, W;ERIKSEN, EF
通讯作者：
ERIKSEN, EF