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Role and Regulation of Mechanotransductive HIF-1α Stabilisation in Periodontal Ligament Fibroblasts

Orthodontic tooth movement (OTM) creates compressive and tensile strain in the periodontal ligament, causing circulation disorders. Hypoxia-inducible factor 1α (HIF-1α) has been shown to be primarily stabilised by compression, but not hypoxia in periodontal ligament fibroblasts (PDLF) during mechani...

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Autores principales: Kirschneck, Christian, Thuy, Magdalena, Leikam, Alexandra, Memmert, Svenja, Deschner, James, Damanaki, Anna, Spanier, Gerrit, Proff, Peter, Jantsch, Jonathan, Schröder, Agnes
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765204/
https://www.ncbi.nlm.nih.gov/pubmed/33333756
http://dx.doi.org/10.3390/ijms21249530
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author Kirschneck, Christian
Thuy, Magdalena
Leikam, Alexandra
Memmert, Svenja
Deschner, James
Damanaki, Anna
Spanier, Gerrit
Proff, Peter
Jantsch, Jonathan
Schröder, Agnes
author_facet Kirschneck, Christian
Thuy, Magdalena
Leikam, Alexandra
Memmert, Svenja
Deschner, James
Damanaki, Anna
Spanier, Gerrit
Proff, Peter
Jantsch, Jonathan
Schröder, Agnes
author_sort Kirschneck, Christian
collection PubMed
description Orthodontic tooth movement (OTM) creates compressive and tensile strain in the periodontal ligament, causing circulation disorders. Hypoxia-inducible factor 1α (HIF-1α) has been shown to be primarily stabilised by compression, but not hypoxia in periodontal ligament fibroblasts (PDLF) during mechanical strain, which are key regulators of OTM. This study aimed to elucidate the role of heparan sulfate integrin interaction and downstream kinase phosphorylation for HIF-1α stabilisation under compressive and tensile strain and to which extent downstream synthesis of VEGF and prostaglandins is HIF-1α-dependent in a model of simulated OTM in PDLF. PDLF were subjected to compressive or tensile strain for 48 h. In various setups HIF-1α was experimentally stabilised (DMOG) or destabilised (YC-1) and mechanotransduction was inhibited by surfen and genistein. We found that HIF-1α was not stabilised by tensile, but rather by compressive strain. HIF-1α stabilisation had an inductive effect on prostaglandin and VEGF synthesis. As expected, HIF-1α destabilisation reduced VEGF expression, whereas prostaglandin synthesis was increased. Inhibition of integrin mechanotransduction via surfen or genistein prevented stabilisation of HIF-1α. A decrease in VEGF expression was observed, but not in prostaglandin synthesis. Stabilisation of HIF-1α via integrin mechanotransduction and downstream phosphorylation of kinases seems to be essential for the induction of VEGF, but not prostaglandin synthesis by PDLF during compressive (but not tensile) orthodontic strain.
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spelling pubmed-77652042020-12-27 Role and Regulation of Mechanotransductive HIF-1α Stabilisation in Periodontal Ligament Fibroblasts Kirschneck, Christian Thuy, Magdalena Leikam, Alexandra Memmert, Svenja Deschner, James Damanaki, Anna Spanier, Gerrit Proff, Peter Jantsch, Jonathan Schröder, Agnes Int J Mol Sci Article Orthodontic tooth movement (OTM) creates compressive and tensile strain in the periodontal ligament, causing circulation disorders. Hypoxia-inducible factor 1α (HIF-1α) has been shown to be primarily stabilised by compression, but not hypoxia in periodontal ligament fibroblasts (PDLF) during mechanical strain, which are key regulators of OTM. This study aimed to elucidate the role of heparan sulfate integrin interaction and downstream kinase phosphorylation for HIF-1α stabilisation under compressive and tensile strain and to which extent downstream synthesis of VEGF and prostaglandins is HIF-1α-dependent in a model of simulated OTM in PDLF. PDLF were subjected to compressive or tensile strain for 48 h. In various setups HIF-1α was experimentally stabilised (DMOG) or destabilised (YC-1) and mechanotransduction was inhibited by surfen and genistein. We found that HIF-1α was not stabilised by tensile, but rather by compressive strain. HIF-1α stabilisation had an inductive effect on prostaglandin and VEGF synthesis. As expected, HIF-1α destabilisation reduced VEGF expression, whereas prostaglandin synthesis was increased. Inhibition of integrin mechanotransduction via surfen or genistein prevented stabilisation of HIF-1α. A decrease in VEGF expression was observed, but not in prostaglandin synthesis. Stabilisation of HIF-1α via integrin mechanotransduction and downstream phosphorylation of kinases seems to be essential for the induction of VEGF, but not prostaglandin synthesis by PDLF during compressive (but not tensile) orthodontic strain. MDPI 2020-12-15 /pmc/articles/PMC7765204/ /pubmed/33333756 http://dx.doi.org/10.3390/ijms21249530 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kirschneck, Christian
Thuy, Magdalena
Leikam, Alexandra
Memmert, Svenja
Deschner, James
Damanaki, Anna
Spanier, Gerrit
Proff, Peter
Jantsch, Jonathan
Schröder, Agnes
Role and Regulation of Mechanotransductive HIF-1α Stabilisation in Periodontal Ligament Fibroblasts
title Role and Regulation of Mechanotransductive HIF-1α Stabilisation in Periodontal Ligament Fibroblasts
title_full Role and Regulation of Mechanotransductive HIF-1α Stabilisation in Periodontal Ligament Fibroblasts
title_fullStr Role and Regulation of Mechanotransductive HIF-1α Stabilisation in Periodontal Ligament Fibroblasts
title_full_unstemmed Role and Regulation of Mechanotransductive HIF-1α Stabilisation in Periodontal Ligament Fibroblasts
title_short Role and Regulation of Mechanotransductive HIF-1α Stabilisation in Periodontal Ligament Fibroblasts
title_sort role and regulation of mechanotransductive hif-1α stabilisation in periodontal ligament fibroblasts
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765204/
https://www.ncbi.nlm.nih.gov/pubmed/33333756
http://dx.doi.org/10.3390/ijms21249530
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