Journal
ORAL DISEASES
Volume 26, Issue 6, Pages 1275-1283Publisher
WILEY
DOI: 10.1111/odi.13341
Keywords
B-cell lymphoma 2; chemokine (C-X-C motif) ligand 8; endothelial cell; nuclear factor-kappa B; stem cells from human exfoliated deciduous teeth; vascular endothelial growth factor
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Funding
- Japan Society for the Promotion of Science [17H04380, 26293405, 24592862, 15K11110, 18K09594]
- Grants-in-Aid for Scientific Research [18K09594, 17H04380, 15K11110, 24592862] Funding Source: KAKEN
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Objectives We aimed to investigate whether the mesenchymal stem cell-endothelial cell crosstalk enhances angiogenic factor expression via nuclear factor-kappa B (NF-kappa B)-dependent mechanisms. Materials and Methods Human dermal microvascular endothelial cells (HDMECs) and stem cells from human exfoliated deciduous teeth (SHEDs) were cocultured for 96 hr, in the presence of NF-kappa B decoy oligodeoxynucleotides (ODNs) or scramble (control). Vascular endothelial cell growth factor (VEGF) and phospho-NF-kappa B p65 were measured with enzyme-linked immunosorbent assay. Angiogenesis-related gene expression was analyzed with microarray analysis followed by real-time polymerase chain reaction. Tube formation assay was conducted in the presence of NF-kappa B decoy. Results The VEGF and phospho-NF-kappa B p65 levels were significantly higher in the coculture with NF-kappa B decoy scramble than in single culture and coculture with NF-kappa B decoy ODN. Microarray analysis of SHEDs and HDMECs with NF-kappa B decoy scramble showed higher expression of proangiogenic genes, Bcl-2, NF-kappa B1, VEGFA, CXCL8, and CXCR1, and lower expression of proapoptotic genes, Bax and Caspase 9, compared to cells with NF-kappa B decoy ODN. Real-time PCR results for Bcl-2 and CXCL8 showed a similar trend. Tube formation assay showed more tube development in the presence of NF-kappa B decoy scramble. Conclusion The SHED-HDMEC crosstalk enhanced proangiogenic factor expression via NF-kappa B-dependent pathways.
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