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Icariin promotes the migration of bone marrow stromal cells via the SDF-1α/HI F-1α/CXCR 4 pathway

Authors Zhu H, Wang X, Han Y, Zhang W, Xin W, Zheng X, Zhang J

Received 12 July 2018

Accepted for publication 17 October 2018

Published 22 November 2018 Volume 2018:12 Pages 4023—4031

DOI https://doi.org/10.2147/DDDT.S179989

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Prof. Dr. Cristiana Tanase


Haiyan Zhu,1–3 Xuxia Wang,1,4 Yuanyuan Han,1,2 Wenjuan Zhang,5 Wei Xin,3 Xiaotao Zheng,3 Jun Zhang1,2

1Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, Shandong Province, China; 2Department of Orthodontics, School of Stomatology, Shandong University, Jinan, Shandong Province, China; 3Department of Stomatology, Weihai Municipal Hospital, Weihai, Shandong Province, China; 4Department of Oral and Maxillofacial Surgery, School of Stomatology, Shandong University, Jinan, Shandong Province, China; 5Department of Stomatology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China

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.

Keywords: cell migration, CXCR4, HIF-1α, SDF-1α, icariin

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