Icariin promotes the migration of bone marrow stromal cells via the SDF-1α/HIF-1α/CXCR4 pathway

PURPOSE: In this study, a series of in vitro experiments were performed to investigate the molecular mechanisms underlying cell migration promoted by icariin (ICA) at low concentrations. MATERIALS AND METHODS: Bone marrow stromal cells (BMSCs) were cultured with different concentrations of ICA to verify whether it can enhance the efficiency of BMSCs migration. Western blot was employed to measure the expression of hypoxia-inducible factor-1α (HIF-1α) and C-X-C chemokine receptor type 4 (CXCR4) at different time points in BMSCs treated with ICA. Subsequently, we evaluated the function of HIF-1α in the expression of CXCR4 and the migration of cells by transfecting plasmid HIF-1α small interfering RNA (siHIF-1α) into BMSCs model. RESULTS: Our data indicated that different concentrations of ICA (10, 1, and 0.1 µM) further enhanced the chemotactic capability of SDF-1α, and the most prominent cell migration stimulatory effect was observed with 1 µM ICA. Furthermore, ICA significantly enhanced the protein levels of CXCR4 and HIF-1α, and this effect was blocked by ICI 12,780 (estrogen receptor antagonis). Moreover, transfection of BMSCs with siHIF-1α reduced CXCR4 expression, suggesting that HIF-1α can regulate the migration of cells by influencing the expression of CXCR4. CONCLUSION: ICA promoted BMSCs migration via the activation of HIF-1α and further regulated the expression of CXCR4, suggesting that ICA might have beneficial effects in stem cell therapy.