The role of HIF-1 alpha in nicotine-induced root and bone resorption during orthodontic tooth movement

Ullrich, Niklas and Schroeder, Agnes and Bauer, Maria and Spanier, Gerrit and Jantsch, Jonathan and Deschner, James and Proff, Peter and Kirschneck, Christian (2021) The role of HIF-1 alpha in nicotine-induced root and bone resorption during orthodontic tooth movement. EUROPEAN JOURNAL OF ORTHODONTICS, 43 (5). pp. 516-526. ISSN 0141-5387, 1460-2210

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Abstract

Background: In orthodontic tooth movement (OTM), pseudo-inflammatory processes occur that are similar to those of nicotine-induced periodontitis. Previous studies have shown that nicotine accelerates OTM, but induces periodontal bone loss and dental root resorption via synergistically increased osteoclastogenesis.This study aimed to investigate the role of hypoxia-inducible factor 1 alpha (HIF-1 alpha) in nicotine-induced osteoclastogenesis during OTM. Materials/Methods: Male Fischer-344 rats were treated with L-Nicotine (1.89 mg/kg/day s.c., N = 10) or NaCl solution (N = 10). After a week of premedication, a NiTi spring was inserted to mesialize the first upper left molar. The extent of dental root resorption, osteoclastogenesis, and HIF-1 alpha protein expression was determined by (immuno)histology, as well as bone volume (BV/TV) and trabecular thickness (TbTh) using mu CT. Receptor activator of nuclear factor of activated B-cells ligand (RANK-L), osteoprotegerin (OPG), and HIF-1 alpha expression were examined at the protein level in periodontal ligament fibroblasts (PDLF) exposed to pressure, nicotine and/or hypoxia, as well as PDLF-induced osteoclastogenesis in co-culture experiments with osteoclast progenitor cells. Results: Nicotine favoured dental root resorptions and osteoclastogenesis during OTM, while BV/TV and TbTh were only influenced by force. This nicotine-induced increase does not appear to be mediated by HIF-1 alpha, since HIF-1 alpha was stabilized by force application and hypoxia, but not by nicotine. The in vitro data showed that the hypoxia-induced increase in RANK-L/OPG expression ratio and PDLF-mediated osteoclastogenesis was less pronounced than the nicotine-induced increase. Conclusions: Study results indicate that the nicotine-induced increase in osteoclastogenesis and periodontal bone resorption during OTM may not be mediated by hypoxic effects or HIF-1 alpha stabilization in the context of nicotine-induced vasoconstriction, but rather by an alternative mechanism.

Item Type: Article
Uncontrolled Keywords: PERIODONTAL-LIGAMENT CELLS; UP-REGULATION; OSTEOCLAST FORMATION; RECEPTOR ACTIVATION; PROSTAGLANDIN E-2; HPDL CELLS; HYPOXIA; EXPRESSION; STRESS; LIPOPOLYSACCHARIDE;
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Kieferorthopädie
Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene
Medicine > Lehrstuhl für Mund-, Kiefer- und Gesichtschirurgie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 02 Aug 2022 12:44
Last Modified: 02 Aug 2022 12:44
URI: https://pred.uni-regensburg.de/id/eprint/46041

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