{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:08:33Z","timestamp":1791284913722,"version":"4.1.0"},"reference-count":62,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2020,12,15]],"date-time":"2020-12-15T00:00:00Z","timestamp":1607990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Forschungsgemeinschaft DFG (German Research Foundation)","award":["KI 2105 \/ 1-2"],"award-info":[{"award-number":["KI 2105 \/ 1-2"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Orthodontic tooth movement (OTM) creates compressive and tensile strain in the periodontal ligament, causing circulation disorders. Hypoxia-inducible factor 1\u03b1 (HIF-1\u03b1) 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\u03b1 stabilisation under compressive and tensile strain and to which extent downstream synthesis of VEGF and prostaglandins is HIF-1\u03b1-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\u03b1 was experimentally stabilised (DMOG) or destabilised (YC-1) and mechanotransduction was inhibited by surfen and genistein. We found that HIF-1\u03b1 was not stabilised by tensile, but rather by compressive strain. HIF-1\u03b1 stabilisation had an inductive effect on prostaglandin and VEGF synthesis. As expected, HIF-1\u03b1 destabilisation reduced VEGF expression, whereas prostaglandin synthesis was increased. Inhibition of integrin mechanotransduction via surfen or genistein prevented stabilisation of HIF-1\u03b1. A decrease in VEGF expression was observed, but not in prostaglandin synthesis. Stabilisation of HIF-1\u03b1 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.<\/jats:p>","DOI":"10.3390\/ijms21249530","type":"journal-article","created":{"date-parts":[[2020,12,15]],"date-time":"2020-12-15T09:12:57Z","timestamp":1608023577000},"page":"9530","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Role and Regulation of Mechanotransductive HIF-1\u03b1 Stabilisation in Periodontal Ligament Fibroblasts"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9473-8724","authenticated-orcid":false,"given":"Christian","family":"Kirschneck","sequence":"first","affiliation":[{"name":"Department of Orthodontics, University Hospital Regensburg, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Thuy","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, University Hospital Regensburg, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Leikam","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, University Hospital Regensburg, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8153-6610","authenticated-orcid":false,"given":"Svenja","family":"Memmert","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, University of Bonn, 53111 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Deschner","sequence":"additional","affiliation":[{"name":"Department of Periodontology and Operative Dentistry, University of Mainz, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2706-398X","authenticated-orcid":false,"given":"Anna","family":"Damanaki","sequence":"additional","affiliation":[{"name":"Department of Periodontology and Operative Dentistry, University of Mainz, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0226-7580","authenticated-orcid":false,"given":"Gerrit","family":"Spanier","sequence":"additional","affiliation":[{"name":"Department of Cranio-Maxillo-Facial Surgery, University Hospital Regensburg, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Proff","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, University Hospital Regensburg, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Jantsch","sequence":"additional","affiliation":[{"name":"Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6010-9831","authenticated-orcid":false,"given":"Agnes","family":"Schr\u00f6der","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, University Hospital Regensburg, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/j.sjbs.2018.03.008","article-title":"Biological aspects of orthodontic tooth movement: A review of literature","volume":"25","author":"Asiry","year":"2018","journal-title":"Saudi J. 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