Sodium butyrate activates ERK to regulate differentiation of mesenchymal stem cells
Sodium butyrate activates ERK to regulate differentiation of mesenchymal stem cells
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DOI：
10.1016/j.bbrc.2007.02.057
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发表时间：
2007-04-20
影响因子：
3.1
通讯作者：
Hung, Shih-Chieh
中科院分区：
文献类型：
--
作者：
Chen, Tain-Hsiung;Chen, Wei-Ming;Hung, Shih-Chieh
已知历史上的脱乙酰酶抑制剂如丁酸钠调节多种细胞的分化。间充质干细胞（MSC）分别在Runx 2和PPAR γ 2的转录控制下分化为成骨细胞和脂肪细胞。丁酸钠如何调控这两种转录因子以指定交替的细胞命运仍然是一个关键问题。丁酸钠刺激成骨分化，并增加Runx 2和Runx 2调控的基因的表达时，细胞诱导进行成骨分化。丁酸钠抑制成脂分化，并降低表达的过氧化物酶体增殖物激活受体γ 2和LPL时，骨髓间充质干细胞处理条件下，促进成脂分化。丁酸钠还可降低NISCs RANKL/OPG基因表达的比值。在丁酸钠存在下诱导的MSC的分析揭示了丁酸钠引起的ERK磷酸化的立即增加。MEK特异性抑制剂PD 98059（而非p38或JNK特异性抑制剂）和显性阴性ERK表达质粒的转染阻断了丁酸钠诱导的MSC分化调节和RANKL/OPG比值的增加。我们的研究结果表明，丁酸钠通过激活ERK调节MSC分化和RANKL/OPG比例，并可用于使用NISCs的体内骨生长。(c)2007年爱思唯尔公司All rights reserved.
Historic deacetylase inhibitors such as sodium butyrate are known to regulate the differentiation of a variety of cells. Mesenchyrnal stem cells (MSCs) differentiate into osteoblasts and adipocytes under transcriptional control of Runx2 and PPAR gamma 2, respectively. How these two transcription factors are regulated by sodium butyrate in order to specify the alternate cell fates remains a pivotal question. Sodium butyrate stimulated osteogenic differentiation and increased expression of Runx2 and genes regulated by Runx2 when cells were induced to undergo osteogenic differentiation. Sodium butyrate suppressed the adipogenic differentiation and decreased the expression of PPAR gamma 2 and LPL when MSCs were treated under conditions that promote adipogenic differentiation. Sodium butyrate also decreased the ratio of RANKL/OPG gene expression by NISCs. Analysis of MSCs induced in the presence of sodium butyrate revealed an immediate increase in ERK phosphorylation by sodium butyrate. The MEK-specific inhibitor, PD98059 but not p38- or JNK-specific inhibitor and the transfection with dominant negative ERK expressing plasmids blocked the sodium butyrate-induced regulation of MSC differentiation and increase in the RANKL/OPG ratio. Our results suggest that sodium butyrate modulates MSC differentiation and the RANKL/OPG ratio via activating ERK, and could be applied for in vivo bone growth using NISCs. (c) 2007 Elsevier Inc. All rights reserved.