Kirschneck, Christian and Thuy, Magdalena and Leikam, Alexandra and Memmert, Svenja and Deschner, James and Damanaki, Anna and Spanier, Gerrit and Proff, Peter and Jantsch, Jonathan and Schroder, Agnes (2020) Role and Regulation of Mechanotransductive HIF-1 alpha Stabilisation in Periodontal Ligament Fibroblasts. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 21 (24): 9530. ISSN , 1422-0067
Full text not available from this repository. (Request a copy)Abstract
Orthodontic tooth movement (OTM) creates compressive and tensile strain in the periodontal ligament, causing circulation disorders. Hypoxia-inducible factor 1 alpha (HIF-1 alpha) 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-1 alpha stabilisation under compressive and tensile strain and to which extent downstream synthesis of VEGF and prostaglandins is HIF-1 alpha-dependent in a model of simulated OTM in PDLF. PDLF were subjected to compressive or tensile strain for 48 h. In various setups HIF-1 alpha was experimentally stabilised (DMOG) or destabilised (YC-1) and mechanotransduction was inhibited by surfen and genistein. We found that HIF-1 alpha was not stabilised by tensile, but rather by compressive strain. HIF-1 alpha stabilisation had an inductive effect on prostaglandin and VEGF synthesis. As expected, HIF-1 alpha destabilisation reduced VEGF expression, whereas prostaglandin synthesis was increased. Inhibition of integrin mechanotransduction via surfen or genistein prevented stabilisation of HIF-1 alpha. A decrease in VEGF expression was observed, but not in prostaglandin synthesis. Stabilisation of HIF-1 alpha 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ORTHODONTIC TOOTH MOVEMENT; INDUCED ANGIOGENESIS; PROSTAGLANDIN E-2; GENE-EXPRESSION; FOCAL ADHESIONS; BONE-RESORPTION; UP-REGULATION; HPDL CELLS; OSTEOCLASTOGENESIS; CYCLOOXYGENASE-2; HIF-1α PDLF; orthodontics; mechanotransduction |
| 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: | 08 Mar 2021 06:42 |
| Last Modified: | 08 Mar 2021 06:42 |
| URI: | https://pred.uni-regensburg.de/id/eprint/43242 |
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