S Memmert1,2, L Gölz3, P Pütz3, A Jäger3, J Deschner4, T Appel5, G Baumgarten6, B Rath-Deschner3, S Frede6, W Götz3. 1. Department of Orthodontics, Center of Dento-Maxillo-Facial Medicine, Faculty of Medicine, University of Bonn, Welschnonnenstr 17, 53111, Bonn, Germany. svenja.memmert@ukb.uni-bonn.de. 2. Section of Experimental Dento-Maxillo-Facial Medicine, Center of Dento-Maxillo-Facial Medicine, Faculty of Medicine, University of Bonn, Bonn, Germany. svenja.memmert@ukb.uni-bonn.de. 3. Department of Orthodontics, Center of Dento-Maxillo-Facial Medicine, Faculty of Medicine, University of Bonn, Welschnonnenstr 17, 53111, Bonn, Germany. 4. Section of Experimental Dento-Maxillo-Facial Medicine, Center of Dento-Maxillo-Facial Medicine, Faculty of Medicine, University of Bonn, Bonn, Germany. 5. Clinic of Oral and Maxillofacial Surgery, Center of Dento-Maxillo-Facial Medicine, Faculty of Medicine, University of Bonn, Bonn, Germany. 6. Clinic and Polyclinic of Anesthesiology and Intensive Care Medicine, Faculty of Medicine, University of Bonn, Bonn, Germany.
Abstract
OBJECTIVES: Different studies suggest that inflammation as well as hypoxia leads to an increase of p53 protein levels. However, the implication of p53 during oral inflammatory processes is still unknown. The aim of this study was therefore to investigate the effect of hypoxia and inflammation on p53 regulation in human periodontium in vitro and in vivo. MATERIALS AND METHODS: Under hypoxic and normoxic conditions, human primary periodontal ligament (PDL) fibroblasts (n = 9) were stimulated with lipopolysaccharides (LPS) from Porphyromonas gingivalis (P.g.), a periodontal pathogenic bacterium. After different time points, cell viability was tested; p53 gene expression, protein synthesis, and activation were measured using quantitative RT-PCR, immunoblotting, and immunofluorescence. Moreover, healthy and inflamed periodontal tissues were obtained from 12 donors to analyze p53 protein in oral inflammatory diseases by immunohistochemistry. RESULTS: LPS-P.g. and hypoxia initially induced a significant upregulation of p53 mRNA expression and p53 protein levels. Nuclear translocation of p53 after inflammatory stimulation supported these findings. Hypoxia first enhanced p53 levels, but after 24 h of incubation, protein levels decreased, which was accompanied by an improvement of PDL cell viability. Immunohistochemistry revealed an elevation of p53 immunoreactivity in accordance to the progression of periodontal inflammation. CONCLUSIONS: Our data indicate that p53 plays a pivotal role in PDL cell homeostasis and seems to be upregulated in oral inflammatory diseases. CLINICAL RELEVANCE: Upregulation of p53 may promote the destruction of periodontal integrity. A possible relationship with carcinogenesis may be discussed.
OBJECTIVES: Different studies suggest that inflammation as well as hypoxia leads to an increase of p53 protein levels. However, the implication of p53 during oral inflammatory processes is still unknown. The aim of this study was therefore to investigate the effect of hypoxia and inflammation on p53 regulation in human periodontium in vitro and in vivo. MATERIALS AND METHODS: Under hypoxic and normoxic conditions, human primary periodontal ligament (PDL) fibroblasts (n = 9) were stimulated with lipopolysaccharides (LPS) from Porphyromonas gingivalis (P.g.), a periodontal pathogenic bacterium. After different time points, cell viability was tested; p53 gene expression, protein synthesis, and activation were measured using quantitative RT-PCR, immunoblotting, and immunofluorescence. Moreover, healthy and inflamed periodontal tissues were obtained from 12 donors to analyze p53 protein in oral inflammatory diseases by immunohistochemistry. RESULTS:LPS-P.g. and hypoxia initially induced a significant upregulation of p53 mRNA expression and p53 protein levels. Nuclear translocation of p53 after inflammatory stimulation supported these findings. Hypoxia first enhanced p53 levels, but after 24 h of incubation, protein levels decreased, which was accompanied by an improvement of PDL cell viability. Immunohistochemistry revealed an elevation of p53 immunoreactivity in accordance to the progression of periodontal inflammation. CONCLUSIONS: Our data indicate that p53 plays a pivotal role in PDL cell homeostasis and seems to be upregulated in oral inflammatory diseases. CLINICAL RELEVANCE: Upregulation of p53 may promote the destruction of periodontal integrity. A possible relationship with carcinogenesis may be discussed.
Authors: B S Michalowicz; D Aeppli; J G Virag; D G Klump; J E Hinrichs; N L Segal; T J Bouchard; B L Pihlstrom Journal: J Periodontol Date: 1991-05 Impact factor: 6.993
Authors: Svenja Memmert; A V B Nogueira; A Damanaki; M Nokhbehsaim; S Eick; T Divnic-Resnik; A Spahr; B Rath-Deschner; A Till; W Götz; J A Cirelli; A Jäger; J Deschner Journal: Clin Oral Investig Date: 2018-02-13 Impact factor: 3.573