Understanding the mechanisms that govern cell fate will lead to the development of techniques for the induction of human mesenchymal stem cell differentiation into desired cell outcomes and the production of an autologous source of tissue for regenerative medicine. Here, we demonstrate that stem cells derived from adult bone marrow grown with 3D pellets take on characteristics similar to human cartilage. The NFAT signaling pathway is primarily linked to cell differentiation and influences chondrogenic differentiation. Based on our previous results that alterations in the expression of the NFATc1 gene affect chondrogenesis, we screened a microarray and identified 29 genes with altered expression, including 13 up-regulated (fold change ≥ 2) and 16 down-regulated (fold change ≤ 2) genes, compared with the control group. We then used RT-PCR to validate the chip data. Gene ontology and pathway analyses were performed on these altered genes. We found that these altered genes function in the complement and coagulation cascades, metabolism, biosynthesis, transcriptional regulation, proteolysis, and intracellular signaling pathways, such as the cytoplasmic calcineurin-dependent signaling pathway, the cyclin-dependent kinase inhibitor 2C signaling pathway, the MAPK signaling pathway, and the insulin signaling pathway. Our study suggests that these pathways may play important roles in chondrogenesis, which could be useful in the design of biomaterials.
Keywords: Human mesenchymal stem cells (hMSCs); gene microarray; nuclear factor of activated T-cells (NFAT).