A potential role for the silent information regulator 2 homologue 1 (SIRT1) in periapical periodontitis

• Published in: International endodontic journal Vol. 51; no. 7; pp. 747 - 757
• Main Authors: Kudo, H., Takeichi, O., Hatori, K., Makino, K., Himi, K., Ogiso, B.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01-07-2018
• Subjects: Adult; Aged; Angiogenesis; Antigens, CD - metabolism; Cadherins; Cadherins - metabolism; Cell adhesion & migration; Cell Proliferation; Dentistry; Endodontics; Endothelial cells; Female; Fluorescent Antibody Technique; Gene expression; Granulomas; Gum disease; Humans; Immunofluorescence; Ki-67 Antigen - metabolism; Lipopolysaccharides; Male; Middle Aged; Neovascularization, Pathologic - metabolism; Periapical Granuloma - metabolism; periapical granulomas; periapical periodontitis; Periapical Periodontitis - metabolism; Periodontitis; Real-Time Polymerase Chain Reaction; Resveratrol; Resveratrol - pharmacology; SIRT1; SIRT1 protein; Sirtuin 1 - metabolism; Statistical analysis; Umbilical vein; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism; wound healing; Young Adult; endothelial cells; periapical periodontitis; wound healing; periapical granulomas; SIRT1; angiogenesis
• ISSN: 0143-2885; 1365-2591
• DOI: 10.1111/iej.12894

Aim
To investigate the role played by silent information regulator 2 homologue 1 (SIRT1) during angiogenesis of periapical periodontitis.
Methodology
Periapical granulomas were subjected to dual‐colour immunofluorescence imaging and real‐time polymerase chain reactions assaying the expression levels of SIRT1, vascular endothelial growth factor (VEGF) and VE‐cadherin. The association between Ki‐67 and SIRT1 expression was also examined. Human umbilical vein endothelial cells (HUVECs) were treated with a combination of lipopolysaccharide and resveratrol (a SIRT1 activator) or sirtinol (a SIRT1 inhibitor); and the levels of mRNAs encoding SIRT1, VEGF and VE‐cadherin were determined. HUVEC tube formation was assayed in the presence of resveratrol or sirtinol. The Mann–Whitney U‐test or the Tukey–Kramer test was used for statistical analysis.
Results
Ki‐67‐expressing cells, including endothelial cells, lay adjacent to SIRT1‐expressing cells in periapical granulomas. In addition, SIRT1‐expressing cells were detected adjacent to VEGF‐expressing cells and VEGF‐ or VE‐cadherin‐expressing endothelial cells. SIRT1, VEGF and VE‐cadherin mRNA expression levels in periapical granulomas were significantly higher (P = 0.0054, 0.0090 and 0.0090, respectively) than those in healthy gingival tissues. HUVECs treated with resveratrol exhibited significantly higher expression of mRNAs encoding SIRT1, VEGF and VE‐cadherin (P = 0.0019, 0.00005 and 0.0045, respectively) compared with controls, but sirtinol inhibited such expression. Resveratrol caused HUVECs to form tube‐like structures, whilst sirtinol inhibited this process.
Conclusions
These findings suggest that SIRT1 may stimulate angiogenesis in periapical granulomas by triggering the proliferation of endothelial cells and inducing VEGF and VE‐cadherin expression.