Notch signaling stimulates osteogenic differentiation of human bone marrow-derived mesenchymal stem cells

Notch signaling is one of the most important pathways mediating cell determination and differentiation. In this study, the roles of Notch signal in the regulation of osteogenic differentiation of human bone marrow mesen-chymal stem cells (hMSCs) were investigated. The expression of Notch1, Jagged1 and DTX1 detected by reverse transcrip-tion polymerase chain reaction (RT-PCR) suggested that Notch signal might exhibit a physiological regulatory role in the differentiation of MSCs. Constitutive expression of the intracellular domain of Notch1 (ICN), the active form of Notch1 protein, can activate Notch signal in cells without ligands binding. hMSCs were isolated, expanded, and in-fected with retrovirus carrying green fluorescent protein (GFP) gene or ICN. Overexpression of ICN in hMSCs re-sulted in enhanced osteogenic differentiation induced by dexamethasone (Dex), which was characterized by an in-crease of cellular alkaline phosphatase (ALP) activity and calcium deposition. These results indicate that Notch stimu-lates differentiation of MSCs into osteoblasts.