Sang-Heng Kok1, Kuo-Liang Hou2, Chi-Yuan Hong3, Ling-Hsiu Chao4, Eddie Hsiang-Hua Lai1, Han-Wei Wang1, Hsiang Yang5, Chia-Tung Shun6, Juo-Song Wang1, Sze-Kwan Lin7. 1. Department of Dentistry, School of Dentistry, College of Medicine, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan. 2. Graduate Institute of Clinical Dentistry, School of Dentistry, College of Medicine, Taipei, Taiwan. 3. Department of Dentistry, School of Dentistry, College of Medicine, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan; College of Bio-Resources and Agriculture, National Taiwan University, Taipei, Taiwan. 4. Department of Dentistry, School of Dentistry, College of Medicine, Taipei, Taiwan. 5. Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan. 6. Department of Forensic Medicine and Pathology, National Taiwan University Hospital, Taipei, Taiwan. 7. Department of Dentistry, School of Dentistry, College of Medicine, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: sklin7400@ntu.edu.tw.
Abstract
INTRODUCTION: Osteoblast apoptosis is important in the regulation of inflammatory bone resorption. Hypoxia resulting from inflammation enhances glycolysis and apoptosis. Sirtuin 6 (SIRT6) is a modulator of glucose metabolism and apoptosis. In the study we assessed the role of SIRT6 in hypoxia-induced glycolysis and apoptosis in osteoblasts, with special attention on the significance of these cellular processes in periapical lesions. METHODS: Human bone marrow-derived osteoblasts were cultured under hypoxia. Expression of lactate dehydrogenase A was examined by Western blot, and production of lactate was measured by colorimetric assay. Cleavage of poly (adenosine diphosphate ribose) polymerase was used as an apoptosis marker and assessed by Western blot. SIRT6 was overexpressed in osteoblasts by lentiviral gene transduction, and then glycolytic and apoptotic responses were studied. In a rat model of bacteria-induced periapical lesions, expressions of SIRT6 and markers of glycolysis and apoptosis in osteoblasts were examined. RESULTS: Hypoxia enhanced lactate dehydrogenase A expression and lactate production in osteoblasts. Poly (adenosine diphosphate ribose) polymerase cleavage was induced by hypoxia or lactate treatment. SIRT6 suppressed hypoxia-augmented glycolysis and inhibited apoptosis induced by hypoxia or lactate treatment. Expression of SIRT6 in osteoblasts was downregulated by hypoxia and inflammatory mediators. Development of periapical lesions in rats was associated with decreased expression of SIRT6 and increased glycolysis and apoptosis in osteoblasts. CONCLUSIONS: Our study suggested that hypoxia-induced apoptosis of osteoblasts is dependent on glycolytic activity. SIRT6 is a negative regulator of inflammation and may alleviate periapical lesions by suppressing osteoblastic glycolysis and apoptosis.
INTRODUCTION: Osteoblast apoptosis is important in the regulation of inflammatory bone resorption. Hypoxia resulting from inflammation enhances glycolysis and apoptosis. Sirtuin 6 (SIRT6) is a modulator of glucose metabolism and apoptosis. In the study we assessed the role of SIRT6 in hypoxia-induced glycolysis and apoptosis in osteoblasts, with special attention on the significance of these cellular processes in periapical lesions. METHODS:Human bone marrow-derived osteoblasts were cultured under hypoxia. Expression of lactate dehydrogenase A was examined by Western blot, and production of lactate was measured by colorimetric assay. Cleavage of poly (adenosine diphosphate ribose) polymerase was used as an apoptosis marker and assessed by Western blot. SIRT6 was overexpressed in osteoblasts by lentiviral gene transduction, and then glycolytic and apoptotic responses were studied. In a rat model of bacteria-induced periapical lesions, expressions of SIRT6 and markers of glycolysis and apoptosis in osteoblasts were examined. RESULTS:Hypoxia enhanced lactate dehydrogenase A expression and lactate production in osteoblasts. Poly (adenosine diphosphate ribose) polymerase cleavage was induced by hypoxia or lactate treatment. SIRT6 suppressed hypoxia-augmented glycolysis and inhibited apoptosis induced by hypoxia or lactate treatment. Expression of SIRT6 in osteoblasts was downregulated by hypoxia and inflammatory mediators. Development of periapical lesions in rats was associated with decreased expression of SIRT6 and increased glycolysis and apoptosis in osteoblasts. CONCLUSIONS: Our study suggested that hypoxia-induced apoptosis of osteoblasts is dependent on glycolytic activity. SIRT6 is a negative regulator of inflammation and may alleviate periapical lesions by suppressing osteoblastic glycolysis and apoptosis.
Authors: Albertas Kriaučiūnas; Rasa Liutkevičienė; Greta Gedvilaitė; Kristė Kaikarytė; Alvita Vilkevičiūtė; Darius Gleiznys; Ingrida Pacauskienė; Gediminas Žekonis Journal: Medicina (Kaunas) Date: 2022-05-12 Impact factor: 2.948
Authors: Maria de Céu Teixeira; Elena Sanchez-Lopez; Marta Espina; Maria Luisa Garcia; Alessandra Durazzo; Massimo Lucarini; Ettore Novellino; Selma B Souto; Antonello Santini; Eliana B Souto Journal: Int J Mol Sci Date: 2019-10-07 Impact factor: 5.923