PMID- 30538428 OWN - NLM STAT- MEDLINE DCOM- 20190326 LR - 20220330 IS - 1177-8881 (Electronic) IS - 1177-8881 (Linking) VI - 12 DP - 2018 TI - Icariin promotes the migration of bone marrow stromal cells via the SDF-1alpha/HIF-1alpha/CXCR4 pathway. PG - 4023-4031 LID - 10.2147/DDDT.S179989 [doi] AB - 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-1alpha (HIF-1alpha) 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-1alpha in the expression of CXCR4 and the migration of cells by transfecting plasmid HIF-1alpha small interfering RNA (siHIF-1alpha) into BMSCs model. RESULTS: Our data indicated that different concentrations of ICA (10, 1, and 0.1 microM) further enhanced the chemotactic capability of SDF-1alpha, and the most prominent cell migration stimulatory effect was observed with 1 microM ICA. Furthermore, ICA significantly enhanced the protein levels of CXCR4 and HIF-1alpha, and this effect was blocked by ICI 12,780 (estrogen receptor antagonis). Moreover, transfection of BMSCs with siHIF-1alpha reduced CXCR4 expression, suggesting that HIF-1alpha can regulate the migration of cells by influencing the expression of CXCR4. CONCLUSION: ICA promoted BMSCs migration via the activation of HIF-1alpha and further regulated the expression of CXCR4, suggesting that ICA might have beneficial effects in stem cell therapy. FAU - Zhu, Haiyan AU - Zhu H AD - Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, Shandong Province, China, zhangj@sdu.edu.cn. AD - Department of Orthodontics, School of Stomatology, Shandong University, Jinan, Shandong Province, China, zhangj@sdu.edu.cn. AD - Department of Stomatology, Weihai Municipal Hospital, Weihai, Shandong Province, China. FAU - Wang, Xuxia AU - Wang X AD - Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, Shandong Province, China, zhangj@sdu.edu.cn. AD - Department of Oral and Maxillofacial Surgery, School of Stomatology, Shandong University, Jinan, Shandong Province, China. FAU - Han, Yuanyuan AU - Han Y AD - Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, Shandong Province, China, zhangj@sdu.edu.cn. AD - Department of Orthodontics, School of Stomatology, Shandong University, Jinan, Shandong Province, China, zhangj@sdu.edu.cn. FAU - Zhang, Wenjuan AU - Zhang W AD - Department of Stomatology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China. FAU - Xin, Wei AU - Xin W AD - Department of Stomatology, Weihai Municipal Hospital, Weihai, Shandong Province, China. FAU - Zheng, Xiaotao AU - Zheng X AD - Department of Stomatology, Weihai Municipal Hospital, Weihai, Shandong Province, China. FAU - Zhang, Jun AU - Zhang J AD - Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, Shandong Province, China, zhangj@sdu.edu.cn. AD - Department of Orthodontics, School of Stomatology, Shandong University, Jinan, Shandong Province, China, zhangj@sdu.edu.cn. LA - eng PT - Journal Article DEP - 20181122 PL - New Zealand TA - Drug Des Devel Ther JT - Drug design, development and therapy JID - 101475745 RN - 0 (CXCL12 protein, rat) RN - 0 (Chemokine CXCL12) RN - 0 (Cxcr4 protein, rat) RN - 0 (Flavonoids) RN - 0 (Hif1a protein, rat) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - 0 (Receptors, CXCR4) RN - VNM47R2QSQ (icariin) SB - IM MH - Animals MH - Bone Marrow Cells/*cytology/drug effects/metabolism MH - Cell Movement/*drug effects MH - Cell Survival/drug effects MH - Cells, Cultured MH - Chemokine CXCL12/*metabolism MH - Dose-Response Relationship, Drug MH - Endoplasmic Reticulum/drug effects/metabolism MH - Flavonoids/*pharmacology MH - Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism MH - Male MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, CXCR4/*metabolism MH - Stromal Cells/cytology/*drug effects/metabolism MH - Structure-Activity Relationship PMC - PMC6254989 OTO - NOTNLM OT - CXCR4 OT - HIF-1alpha OT - SDF-1alpha OT - cell migration OT - icariin COIS- Disclosure The authors report no conflicts of interest in this work. EDAT- 2018/12/13 06:00 MHDA- 2019/03/27 06:00 PMCR- 2018/11/22 CRDT- 2018/12/13 06:00 PHST- 2018/12/13 06:00 [entrez] PHST- 2018/12/13 06:00 [pubmed] PHST- 2019/03/27 06:00 [medline] PHST- 2018/11/22 00:00 [pmc-release] AID - dddt-12-4023 [pii] AID - 10.2147/DDDT.S179989 [doi] PST - epublish SO - Drug Des Devel Ther. 2018 Nov 22;12:4023-4031. doi: 10.2147/DDDT.S179989. eCollection 2018.