Inhibition of transforming growth factor-β signaling pathway enhances the osteogenic differentiation of unrestricted somatic stem cells.

Abstract

In recent years, extensive studies have been performed to enhancestem cell-based therapies for bone and cartilage repair. Among various sources of stem cells,cord blood-derived unrestricted somatic stem cells (USSCs) seem to be the most appropriate option for an autologous transplantation. Among different signaling pathways, the transforming growth factor-β (TGF-β) pathway is shown as an important regulator of proliferation and osteogenic differentiation inosteoblast progenitors as well as mesenchymal stem cells. Due to its contradictory and temporally variable effects on different cell types, we sought to investigate whether and how the TGF-β signaling pathway regulates the osteogenic differentiation of the USSCs. Therefore, in the current study, wetreated USSCs with the recombinant protein TGF-β1 (1 ng/mL) and showed that the expression of matrix metalloproteinase 9, a well-known effector in this pathway, was significantly induced, indicating that the TGF-β signaling pathway is active in USSCs. Then we applied a TGF-β receptor antagonist (SB431542; 10 μM) to the osteogenic media cultured USSCs for single periods of 3.5 days within the 21-day differentiation period starting at day 0, 3.5, 7, 10.5, 14, and 17.5. The expression analysis results of the of the osteogenic marker runt-related transcription factor 2 as well as the production of bone matrix showed that SB431542 induced the osteogenic differentiation of USSCs more significantly during the early stage of differentiation, suggesting that the TGF-β pathway temporally regulates the osteogenic differentiation of USSCs.