BMP3 Alone and Together with TGF-β Promote the Differentiation of Human Mesenchymal Stem Cells into a Nucleus Pulposus-Like Phenotype.
BMP3 Alone and Together with TGF-β Promote the Differentiation of Human Mesenchymal Stem Cells into a Nucleus Pulposus-Like Phenotype.
复制标题
BMP3单独和与TGF-β一起促进人间充质干细胞分化为髓核样表型
DOI：
10.3390/ijms160920344
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发表时间：
2015-08-27
影响因子：
5.6
通讯作者：
Chen Q
中科院分区：
文献类型：
--
作者：
Zhou X;Tao Y;Liang C;Zhang Y;Li H;Chen Q
人间充质干细胞（MSCs）在特定的刺激条件下具有向髓核（NP）样细胞分化的潜力。迄今为止，骨形态发生蛋白3 （bone morphogenetic protein 3, BMP3）以及BMP3与转化生长因子(TGF)-β的鸡尾酒作用对MSC增殖分化的影响尚不清楚。因此，本研究旨在澄清这些未知因素。以不同梯度的BMP3和BMP3/TGF-β培养MSCs，并与基础培养基和TGF-β培养基培养的MSCs进行比较。通过检测细胞增殖、糖胺聚糖（GAG）含量、基因表达和信号蛋白，评估BMP3和BMP3/TGF-β对MSCs的影响。添加BMP3后细胞数量和GAG含量呈剂量依赖性增加。与COL1A1、ALP、OPN和COMP相比，BMP3和TGF-β诱导后COL2A1、ACAN、SOX9和KRT19的表达增加，Smad3的磷酸化被BMP3和TGF-β上调，但BMP3不影响细胞外信号调节激酶（ERK） 1/2和c-Jun n末端激酶（JNK）的磷酸化。我们的研究结果表明，BMP3通过增加细胞数量和特异性基因表达来促进MSC的增殖和向np样细胞的分化，并可能与TGF-β诱导的积极作用协同作用。这些作用可能与TGF-β信号通路的激活有关。
Human mesenchymal stem cells (MSCs) have the potential to differentiate into nucleus pulposus (NP)-like cells under specific stimulatory conditions. Thus far, the effects of bone morphogenetic protein 3 (BMP3) and the cocktail effects of BMP3 and transforming growth factor (TGF)-β on MSC proliferation and differentiation remain obscure. Therefore, this study was designed to clarify these unknowns. MSCs were cultured with various gradients of BMP3 and BMP3/TGF-β, and compared with cultures in basal and TGF-β media. Cell proliferation, glycosaminoglycan (GAG) content, gene expression, and signaling proteins were measured to assess the effects of BMP3 and BMP3/TGF-β on MSCs. Cell number and GAG content increased upon the addition of BMP3 in a dose-dependent manner. The expression of COL2A1, ACAN, SOX9, and KRT19 increased following induction with BMP3 and TGF-β, in contrast to that of COL1A1, ALP, OPN, and COMP. Smad3 phosphorylation was upregulated by BMP3 and TGF-β, but BMP3 did not affect the phosphorylation of extracellular-signal regulated kinase (ERK) 1/2 or c-Jun N-terminal kinase (JNK). Our results reveal that BMP3 enhances MSC proliferation and differentiation into NP-like cells, as indicated by increased cell numbers and specific gene expressions, and may also cooperate with TGF-β induced positive effects. These actions are likely related to the activation of TGF-β signaling pathway.