Chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells treated by GSK-3 inhibitors
Chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells treated by GSK-3 inhibitors
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DOI：
10.1007/s00418-013-1121-x
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发表时间：
2013-12-01
影响因子：
2.3
通讯作者：
Shahhoseini, Maryam
中科院分区：
文献类型：
--
作者：
Eslaminejad, Mohamadreza Baghaban;Karimi, Negar;Shahhoseini, Maryam
研究间充质干细胞（MSCs）的软骨分化将是特别有趣的，因为基于细胞的软骨缺陷治疗的一种策略强调使用处于分化状态的细胞。本研究试图评估两种众所周知的糖原合成酶激酶3抑制剂，包括氯化锂（LiCl）和SB216763对人骨髓源性MSC （hMSC）软骨培养的影响。将传代3 MSCs凝聚成小颗粒，根据补充软骨培养基分为以下组：转化生长因子(TGF)- β 1、TGF- β 1 + LiCl、TGF- β 1 + SB216763、TGF- β 3、TGF- β 3 + LiCl和TGF- β 3 + SB216763。培养21天后，分析Sox9、aggrecan、collagen II、β -catenin和axin基因的表达情况。在某些培养中，还测量了软骨基质中糖胺聚糖（GAG）的沉积。在MSC软骨培养中，LiCl和SB216763以及tgf - β的存在导致了软骨特异性基因的上调。tgf - β 3明显优于tgf - β 1。根据我们的研究结果，SB216763在上调软骨特异性基因方面更有效。这些成软骨作用似乎是通过Wnt信号通路介导的，因为β -连环蛋白和轴蛋白分别倾向于上调和下调。在SB216763 + tgf - β 3的培养中，GAG沉积量显著增加（P < 0.05）。综上所述，在hMSC软骨培养中添加SB216763或LiCl均可上调软骨特异性基因的表达，并增强培养物中的GAG沉积。
A study of the cartilage differentiation of mesenchymal stem cells (MSCs) would be of particular interest since one strategy for cell-based treatment of cartilage defects emphasizes the use of cells that are in a differentiated state. The present study has attempted to evaluate the effects of two well-known glycogen synthase kinase-3 inhibitors, including lithium chloride (LiCl) and SB216763 on a human marrow-derived MSC (hMSC) chondrogenic culture. Passaged-3 MSCs were condensed into small pellets and cultivated in the following groups based on the supplementation of chondrogenic medium: transforming growth factor (TGF)-beta 1, TGF-beta 1 + LiCl, TGF-beta 1 + SB216763, TGF-beta 3, TGF-beta 3 + LiCl, and TGF-beta 3 + SB216763. The cultures were maintained for 21 days and then analyzed for expression of Sox9, aggrecan, collagen II, beta-catenin, and axin genes. Deposition of glycosaminoglycan (GAG) in the cartilage matrix was also measured for certain cultures. The presence of both LiCl and SB216763 along with TGF-beta in the MSC chondrogenic culture led to the up-regulation of cartilage-specific genes. TGF-beta 3 appeared much better than TGF-beta 1. Based on our findings, SB216763 was more effective in up-regulation of cartilage-specific genes. These chondrogenic effects appeared to be mediated through the Wnt signaling pathway since beta-catenin and axin tended to be up-regulated and down-regulated, respectively. In the culture with SB216763 + TGF-beta 3, significantly more GAG was deposited (P < 0.05). In conclusion, addition of either SB216763 or LiCl to hMSC chondrogenic culture up-regulates cartilage-specific gene expression and enhances GAG deposition in the culture.