{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T19:41:12Z","timestamp":1789846872529,"version":"4.0.1"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2012,1,20]],"date-time":"2012-01-20T00:00:00Z","timestamp":1327017600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Orthod Craniofacial Res"],"published-print":{"date-parts":[[2012,2]]},"abstract":"<jats:sec><jats:label\/><jats:p>Dandajena T. C., Ihnat M. A., Disch B., Thorpe J., Currier G. F. Hypoxia triggers a HIF\u2010mediated differentiation of peripheral blood mononuclear cells into osteoclasts. \u2028<jats:italic>Orthod Craniofac Res<\/jats:italic> 2012;<jats:bold>15<\/jats:bold>:1\u20139 \u00a9 John Wiley &amp; Sons A\/S<\/jats:p><\/jats:sec><jats:sec><jats:title>Structured Abstract<\/jats:title><jats:p><jats:bold>Background\u2002\u2013\u2002<\/jats:bold> The source and mechanisms leading to osteoclast (OC) generation during tooth movement are not clearly understood. We hypothesized that during tooth movement, OC differentiate from peripheral blood mononuclear cells (PBMNC) downstream of the global hypoxia\u2010inducible transcription factor hypoxia\u2010inducible factor (HIF)\u20101\u03b1.<\/jats:p><jats:p><jats:bold>Objective\u2002\u2013\u2002<\/jats:bold> The objective of this study was to demonstrate up\u2010regulation of OC growth factors from osteoblasts (OB) and subsequent conversion of PBMNC into functional OC under hypoxic stress.<\/jats:p><jats:p><jats:bold>Material and Methods\u2002\u2013\u2002<\/jats:bold> Human primary PBMNC were cocultured with\/without OB and subjected to either hypoxia (2.5% O<jats:sub>2<\/jats:sub>) or normoxia (21% O<jats:sub>2<\/jats:sub>) over 14\u2003days. Levels of HIF, vascular endothelial growth factor (VEGF) and receptor activator for nuclear factor kappa\u2010\u03b2 ligand (RANKL) were measured. Conversion of PBMNC into OC was measured using resorption and TRAP assays.<\/jats:p><jats:p><jats:bold>Results\u2002\u2013\u2002<\/jats:bold> Functional OC were only observed in response to hypoxia during coculture of PBMNC and OB and only after up\u2010regulation of HIF, VEGF and RANKL in the hypoxic conditions. YC\u20101, a HIF inhibitor, reduced OC formation in response to hypoxia.<\/jats:p><jats:p><jats:bold>Conclusion\u2002\u2013\u2002<\/jats:bold> Hypoxia triggers the differentiation of PBMNC into functional OC in the presence of OB in a HIF\u2010dependent manner as would occur during orthodontic loading of the periodontal ligament space.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1601-6343.2011.01530.x","type":"journal-article","created":{"date-parts":[[2012,1,20]],"date-time":"2012-01-20T12:09:27Z","timestamp":1327061367000},"page":"1-9","source":"Crossref","is-referenced-by-count":44,"title":["Hypoxia triggers a HIF\u2010mediated differentiation of peripheral blood mononuclear cells into osteoclasts"],"prefix":"10.1111","volume":"15","author":[{"given":"T. C.","family":"Dandajena","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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