S Memmert1,2, A V B Nogueira3, A Damanaki3, M Nokhbehsaim4, B Rath-Deschner5, W Götz5, L Gölz6,7, J A Cirelli8, A Till9, A Jäger5, J Deschner3. 1. Department of Orthodontics, Center of Dento-Maxillo-Facial 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, University of Bonn, Bonn, Germany. svenja.memmert@ukb.uni-bonn.de. 3. Department of Periodontology and Operative Dentistry, University Medical Center of the Johannes Gutenberg University, Mainz, Germany. 4. Section of Experimental Dento-Maxillo-Facial Medicine, Center of Dento-Maxillo-Facial Medicine, University of Bonn, Bonn, Germany. 5. Department of Orthodontics, Center of Dento-Maxillo-Facial Medicine, University of Bonn, Welschnonnenstr. 17, 53111, Bonn, Germany. 6. Department of Orthodontics and Orofacial Orthopedics, University of Erlangen, Erlangen, Germany. 7. Institute of Human Genetics, University Hospital of Bonn, Bonn, Germany. 8. Department of Diagnosis and Surgery, School of Dentistry at Araraquara, University Estadual Paulista-UNESP, Araraquara, Brazil. 9. Institute of Reconstructive Neurobiology, Life and Brain Center, University of Bonn, Bonn, Germany.
Abstract
PURPOSE: Orthodontic treatment is based on the principle of force application to teeth and subsequently to the surrounding tissues and periodontal cells. Sequestosome 1 (SQSTM1) is a well-known marker for autophagy, which is an important cellular mechanism of adaptation to stress. The aim of this study was to analyze whether biomechanical loading conditions regulate SQSTM1 in periodontal cells and tissues, thereby providing further information on the role of autophagy in orthodontic tooth movement. METHODS: Periodontal ligament (PDL) fibroblasts were exposed to cyclic tensile strain of low magnitude (3%, CTSL), and the regulation of autophagy-associated targets was determined with an array-based approach. SQSTM1 was selected for further biomechanical loading experiments with dynamic and static tensile strain and assessed via real-time polymerase chain reaction (RT-PCR) and immunoblotting. Signaling pathways involved in SQSTM1 activation were analyzed by using specific inhibitors, including an autophagy inhibitor. Finally, SQSTM1 expression was analyzed in gingival biopsies and histological sections of rats in presence and absence of orthodontic forces. RESULTS: Multiple autophagy-associated targets were regulated by CTSL in PDL fibroblasts. All biomechanical loading conditions tested increased the SQSTM1 expression significantly. Stimulatory effects of CTSL on SQSTM1 expression were diminished by inhibition of the c‑Jun N‑terminal kinase (JNK) pathway and of autophagy. Increased SQSTM1 levels after CTSL were confirmed by immunoblotting. Orthodontic force application also led to significantly elevated SQTSM1 levels in the gingiva and PDL of treated animals as compared to control. CONCLUSIONS: Our in vitro and in vivo findings provide evidence of a role of SQSTM1 and thereby autophagy in orthodontic tooth movement.
PURPOSE: Orthodontic treatment is based on the principle of force application to teeth and subsequently to the surrounding tissues and periodontal cells. Sequestosome 1 (SQSTM1) is a well-known marker for autophagy, which is an important cellular mechanism of adaptation to stress. The aim of this study was to analyze whether biomechanical loading conditions regulate SQSTM1 in periodontal cells and tissues, thereby providing further information on the role of autophagy in orthodontic tooth movement. METHODS: Periodontal ligament (PDL) fibroblasts were exposed to cyclic tensile strain of low magnitude (3%, CTSL), and the regulation of autophagy-associated targets was determined with an array-based approach. SQSTM1 was selected for further biomechanical loading experiments with dynamic and static tensile strain and assessed via real-time polymerase chain reaction (RT-PCR) and immunoblotting. Signaling pathways involved in SQSTM1 activation were analyzed by using specific inhibitors, including an autophagy inhibitor. Finally, SQSTM1 expression was analyzed in gingival biopsies and histological sections of rats in presence and absence of orthodontic forces. RESULTS: Multiple autophagy-associated targets were regulated by CTSL in PDL fibroblasts. All biomechanical loading conditions tested increased the SQSTM1 expression significantly. Stimulatory effects of CTSL on SQSTM1 expression were diminished by inhibition of the c‑Jun N‑terminal kinase (JNK) pathway and of autophagy. Increased SQSTM1 levels after CTSL were confirmed by immunoblotting. Orthodontic force application also led to significantly elevated SQTSM1 levels in the gingiva and PDL of treated animals as compared to control. CONCLUSIONS: Our in vitro and in vivo findings provide evidence of a role of SQSTM1 and thereby autophagy in orthodontic tooth movement.
Authors: Andressa Vilas Boas Nogueira; Marjan Nokhbehsaim; Sigrun Eick; Christoph Bourauel; Andreas Jäger; Søren Jepsen; Joni Augusto Cirelli; James Deschner Journal: Clin Oral Investig Date: 2013-02-13 Impact factor: 3.573
Authors: Kim Blawat; Alexandra Mayr; Miriam Hardt; Christian Kirschneck; Marjan Nokhbehsaim; Christian Behl; James Deschner; Andreas Jäger; Svenja Memmert Journal: Int J Mol Sci Date: 2020-12-11 Impact factor: 5.923