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Regulation of tyrosine hydroxylase in periodontal fibroblasts and tissues by obesity-associated stimuli

Memmert, Svenja, Damanaki, Anna, Nogueira, Andressa V. B., Nokhbehsaim, Marjan, Götz, Werner, Cirelli, Joni A., Rath-Deschner, Birgit, Jäger, Andreas, Deschner, James
Cell and tissue research 2019 v.375 no.3 pp. 619-628
analysis of variance, biopsy, catalytic activity, catecholamines, enzyme-linked immunosorbent assay, fibroblasts, gene expression, gene expression regulation, humans, immunocytochemistry, immunohistochemistry, leptin, ligaments, nicotinamide phosphoribosyltransferase, obesity, patients, periodontitis, protein content, quantitative polymerase chain reaction, rats, tyrosine 3-monooxygenase
Tyrosine hydroxylase (TH) catalyzes the rate-limiting step in the synthesis of catecholamines and has been connected to aggravated progression of periodontal disease under chronic stress. Obesity is known to increase the risk of periodontitis and adipokines have been suggested to be a pathomechanistic link. This study examines if obesity-associated stimuli have regulatory effects on TH levels in periodontal cells and tissues. Human periodontal ligament fibroblasts were cultured in the presence of leptin or visfatin for up to 2 days. Untreated cells served as control. TH regulation was analyzed by real-time PCR, immunocytochemistry and ELISA. TH gene expression in periodontal tissues of normal-weight and obese rodents was determined. Examination of gingival biopsies from rats and patients with and without periodontal disease was performed by real-time PCR or immunohistochemistry. For statistics, ANOVA and post hoc tests were applied (p < 0.05). In vitro, TH gene expression and protein levels were increased by leptin and visfatin. In vivo, TH gene expression was upregulated in periodontal tissues of obese rodents as compared to normal-weight animals. Additionally, increased TH gene expression was found in rat gingival biopsies with experimental periodontitis. Human gingival biopsies from sites of periodontitis confirmed the animal data by demonstrating elevated TH levels at periodontally diseased sites. This study provides original evidence that obesity-associated stimuli induce a TH upregulation in periodontal cells and tissues. Since TH levels were also increased at periodontitis sites, our in vitro and animal findings suggest that this enzyme could represent a pathomechanism whereby obesity contributes to periodontitis.