Elucidation of adipogenic differentiation regulatory mechanism in human maxillary/mandibular bone marrow-derived stem cells

Abstract

Mesenchymal stem cells (MSCs) are pluripotent stem cells present in various tissues. Previous studies have shown that maxillary/mandibular bone marrow-derived MSCs (MBMSCs) scarcely differentiate into adipocytes. However, the regulatory molecular mechanisms underlying adipogenic differentiation of MBMSCs remain unknown. We investigated the underlying molecular mechanisms that regulate adipogenic differentiation of MBMSCs. We observed no significant differences in cell surface antigen profiles and stem cell marker gene expression in MBMSCs and iliac bone marrow-derived MSCs (IBMSCs). MBMSCs and IBMSCs displayed similar osteogenic and chondrogenic differentiation potentials, whereas MBMSCs showed significantly lower lipid accumulation, adipocyte marker gene expression, and intracellular glucose uptake than that showed by IBMSCs. Expression of CCAAT/enhancer binding protein β (C/EBPβ), C/EBPδ, early B-cell factor 1 (Ebf-1), and Krüppel-like factor 5 (KLF5), which are transcription factors expressed early in adipogenic differentiation, was suppressed in MBMSCs compared to that in IBMSCs. Peroxisome proliferator-activated receptor-γ (PPARγ) and C/EBPα, which play important roles in the terminal differentiation of preadipocytes into mature adipocytes, were increased during adipogenic differentiation in MBMSCs and IBMSCs; however, the expression level of these genes in MBMSCs was lower than that in IBMSCs. Furthermore, the level of zinc finger protein 423 (Zfp423), which is involved in the commitment of undifferentiated MSCs to the adipocyte lineage, was significantly lower in undifferentiated MBMSCs than that in IBMSCs. These data indicate that MBMSCs are negatively regulated in the commitment of undifferentiated MSCs to the adipocyte lineage (preadipocytes) and in terminal differentiation into mature adipocytes. These results may elucidate the site-specific characteristics of MBMSCs.