Comparative profiling of chondrogenic differentiation of mesenchymal stem cells (MSCs) driven by two different growth...

This study aimed to investigate the mechanism of nerve growth factor (NGF) from cobra venom and human transforming growth factor-β1 (TGF-β1) on the chondrogenic induction of mesenchymal stem cells (MSCs). NGF and TGF-β1 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-β1. PI3K-AKT signalling pathway is commonly involved in the chondrogenesis of MSCs induced by NGF and TGF-β1. However, the expression levels of the genes in the PI3K-AKT signalling pathway were significantly higher in NGF group than that in the TGF-β1 group. In the process of chondrogenesis of MSCs induced by NGF and TGF-β1, 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-β1. TGF-β1 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-β1. 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-β1 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-β1 caused osteophyte formation by activating THBS1 and THBS2. These might be the reason why NGF could promote cartilage differentiation more specifically.