Cerium promotes bone marrow stromal cells migration and osteogenic differentiation via Smad1/5/8 signaling pathway

Cerium (Ce), one of the lanthanides (Ln), displays a variety of biochemical and physiological effects. However, the potential effect and mechanism of Ce on bone metabolism are not well understood. In this study, we investigated the putative role of Ce in regulating the migration and osteogenic differentiation of bone marrow stromal cells (BMSCs) and the underlying mechanism. The results indicated that Ce promoted BMSCs viability and ALP activity at lower concentrations (0.001 μM), and decreased the viability and ALP activity of BMSCs at higher concentrations (10 μM). Ce could also affect the expression of osteogenic transcription factors (Runx2, Satb2 and OCN) in BMSCs. Our results also showed that Ce promoted migration of BMSCs by increasing SDF-1 mRNA expression. As the Smad-dependent BMP signaling pathway plays an important role in migration and osteogenic differentiation of BMSCs, our results are in agreement with Ce promoting the phosphorylation of Smad1/5/8 and translocating to the nucleus by increase BMP2 expression. The activity of p-Smad1/5/8 increased SDF-1 and Runx2 expression level in BMSCs. In conclusion, our results support the notion that Ce promoted migration and osteogenic differentiation of BMSCs by Smad1/5/8 signaling pathway.