The balance of osteogenic and adipogenic differentiation in human mesenchymal stem cells by matrices that mimic stepwise tissue development.

The disruption of balance between osteogenesis and adipogenesis of mesenchymal stem cells (MSCs) leads to the disorders such as osteoporosis. Controlling the balance of these processes during MSC differentiation is important to maintain bone homeostasis. The extracellular microenvironment, especially the extracellular matrix (ECM), plays an important role in regulating MSC differentiation. Here, we investigated the role of ECM in controlling the balance between osteogenesis and adipogenesis of MSCs with matrices that mimic the stepwise tissue development of ECM during osteogenesis and adipogenesis. The osteogenesis of MSCs was enhanced by matrices with upregulated RUNX2 expression and suppressed PPARG expression, which mimic the attributes of the ECM during the early stages of osteogenesis. MSC adipogenesis was enhanced by matrices with suppressed expression of RUNX2, MSX2, and TAZ, which mimics the characteristics of ECM during the early stages of adipogenesis. These results showed that ECM may regulate the expression of various transcription factors to control the balance of osteogenesis and adipogenesis of MSCs. Tissue- and stage-specific ECM are required to control differentiation of MSCs into a specific cell types.