Comparative profiling of chondrogenic differentiation of mesenchymal stem cells (MSCs) driven by two different growth factors
Comparative profiling of chondrogenic differentiation of mesenchymal stem cells (MSCs) driven by two different growth factors
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两种不同生长因子驱动的间充质干细胞（MSC）软骨分化的比较分析
DOI：
10.1002/cbf.3404
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发表时间：
2019-07-01
影响因子：
3.6
通讯作者：
Zhao, Jinmin
中科院分区：
文献类型：
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作者：
Zhan, Xintang;Cai, Peian;Zhao, Jinmin
本研究旨在探讨眼镜蛇毒神经生长因子（NGF）和人转化生长因子-β 1（TGF-β 1）对骨髓间充质干细胞（MSCs）软骨诱导的作用机制。用NGF和TGF-β 1诱导兔骨髓间充质干细胞软骨形成7天。提取总RNA用于mRNA测序。通过差异表达基因（DEG）、基因本体（GO）、KEGG通路富集和PPI网络分析筛选特异性信号通路和靶基因。采用实时荧光定量聚合酶链反应（qRT-PCR）进一步确认相关靶基因。结果表明，与TGF-β 1相比，NGF可显著促进透明软骨特异性基因（II型胶原α 1链，COL 2A 1）的表达。PI 3 K-AKT信号通路通常参与由NGF和TGF-β 1诱导的MSC的软骨形成。而NGF组PI 3 K-AKT信号通路基因的表达水平明显高于TGF-β 1组。在NGF和TGF-β 1诱导的MSCs软骨形成过程中，整合素（integrin，ITGAs）是激活PI 3 K-AKT信号通路的靶向中枢基因。在MSCs向软骨细胞分化的过程中，NGF比TGF-β 1能激活更多的增殖和分化基因。TGF-β 1通过靶向可能促进骨赘形成的血小板反应蛋白（THBS 1）和THBS 2促进血管生成。PI 3 K-AKT是软骨细胞分化的关键信号通路。NGF可以更高水平地激活PI 3 K-AKT信号通路，并且与TGF-β 1相比，NGF对促进软骨细胞特定基因的表达具有更高的特异性。本研究比较了两种不同的生长因子对MSCs软骨分化的促进作用，发现了一些异同。我们发现，在MSC的软骨形成过程中，NGF和TGF-β 1都可以通过靶向ITGA激活PI 3 K-AKT信号通路（其在NGF中的表达更高）。但在MSCs的软骨形成过程中，NGF可激活更多的增殖和分化基因，而TGF-β 1则通过激活THBS 1和THBS 2而导致骨赘形成。这可能是NGF促进软骨分化的特异性更强的原因。
This study aimed to investigate the mechanism of nerve growth factor (NGF) from cobra venom and human transforming growth factor-beta 1 (TGF-beta 1) on the chondrogenic induction of mesenchymal stem cells (MSCs). NGF and TGF-beta 1 were used to induce chondrogenesis of MSCs from rabbits for 7 days. Total RNA was extracted for mRNA sequencing. Differentially expressed genes (DEGs), gene ontology (GO), KEGG pathway enrichment, and PPI network analysis were conducted to screen the specific signalling pathways and target genes. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to further confirm the relative target genes. The results showed that NGF could significantly promote the expression of hyaline cartilage specific genes (collagen type II alpha 1 chain, COL2A1) compared with TGF-beta 1. PI3K-AKT signalling pathway is commonly involved in the chondrogenesis of MSCs induced by NGF and TGF-beta 1. However, the expression levels of the genes in the PI3K-AKT signalling pathway were significantly higher in NGF group than that in the TGF-beta 1 group. In the process of chondrogenesis of MSCs induced by NGF and TGF-beta 1, integrin (ITGAs) were the targeted hub genes to activate the PI3K-AKT signalling pathway. NGF could activate more proliferation and differentiation genes in the process of chondrogenesis of MSCs than TGF-beta 1. TGF-beta 1 promoted angiogenesis by targeting the thrombospondin (THBS1) and THBS2 which might contribute to the osteophyte formation. PI3K-AKT was the crucial signalling pathway for chondrogenic differentiation. NGF could activate the PI3K-AKT signalling pathway to a higher level, and NGF had more specificity for promoting expression of specific genes of chondrocyte compared with TGF-beta 1. Significance of the study In our study, we compared two different growth factors in promoting cartilage differentiation of MSCs and found some similarities and differences. We revealed that both NGF and TGF-beta 1 could activate the PI3K-AKT signalling pathway (the expression of it in NGF was higher) by targeting the ITGAs in the process of chondrogenesis from MSCs. However, NGF could activate more proliferation and differentiation genes in the process of chondrogenesis of MSCs, whereas TGF-beta 1 caused osteophyte formation by activating THBS1 and THBS2. These might be the reason why NGF could promote cartilage differentiation more specifically.