{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T06:15:04Z","timestamp":1772086504873,"version":"3.50.1"},"reference-count":43,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,3,20]],"date-time":"2019-03-20T00:00:00Z","timestamp":1553040000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100002152","name":"International Trachoma Initiative","doi-asserted-by":"publisher","award":["1085_2015"],"award-info":[{"award-number":["1085_2015"]}],"id":[{"id":"10.13039\/100002152","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Periodontal Research"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:sec><jats:title>Background and objective<\/jats:title><jats:p>A key factor in the modulation of angiogenesis as well as in bone resorption is angiopoietin\u2010like 4. However, the role of angiopoietin\u2010like 4 in periodontal tissue is unknown. Here, we hypothesized that hypoxia and the hypoxia mimetic agent L\u2010mimosine can induce the production of angiopoietin\u2010like 4 in periodontal fibroblasts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Human periodontal ligament fibroblasts (<jats:styled-content style=\"fixed-case\">PDLF<\/jats:styled-content>) were cultured in monolayer and spheroid cultures. The cultures were incubated in the presence of hypoxia or L\u2010mimosine. Angiopoietin\u2010like 4 <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> and protein levels were measured by <jats:styled-content style=\"fixed-case\">qPCR<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">ELISA<\/jats:styled-content>, respectively. Also, the impact of Lipopolysaccharides of <jats:italic>E.\u00a0coli<\/jats:italic> and <jats:italic>P.\u00a0gingivalis<\/jats:italic>, interleukin (<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>)\u20101\u03b2 and tumor necrosis factor (<jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>)\u03b1 was evaluated. Furthermore, we tested dependency on hypoxia\u2010inducible factor (HIF)\u20101 activity by Western blotting for <jats:styled-content style=\"fixed-case\">HIF<\/jats:styled-content>\u20101 and inhibitor studies with echinomycin. Potential autocrine effects were assessed by exposure of <jats:styled-content style=\"fixed-case\">PDLF<\/jats:styled-content> to recombinant angiopoietin\u2010like 4 in full length, C\u2010terminal and N\u2010terminal fragments. The impact on viability, <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> synthesis, alkaline phosphatase, and matrix mineralization was evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Both hypoxia and L\u2010mimosine elevated angiopoietin\u2010like 4 <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> and protein levels in monolayer cultures of <jats:styled-content style=\"fixed-case\">PDLF<\/jats:styled-content>. <jats:styled-content style=\"fixed-case\">HIF<\/jats:styled-content>\u20101 was elevated after both hypoxia and L\u2010mimosine treatment. <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> IL<\/jats:styled-content>\u20101\u03b2, and <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u03b1 did not modulate angiopoietin\u2010like 4 levels significantly. Addition of echinomycin in the cultures inhibited the production of angiopoietin\u2010like 4. In spheroid cultures of <jats:styled-content style=\"fixed-case\">PDLF<\/jats:styled-content>, the increase did not reach the level of significance at <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> and protein levels. Angiopoietin\u2010like 4 in full length, C\u2010terminal, and N\u2010terminal fragments did not modulate viability, <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> synthesis, alkaline phosphatase, and matrix mineralization.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Overall, we found that hypoxia and the hypoxia mimetic agent L\u2010mimosine can stimulate angiopoietin\u2010like 4 production in monolayer cultures of <jats:styled-content style=\"fixed-case\">PDLF<\/jats:styled-content>. This increase depends on <jats:styled-content style=\"fixed-case\">HIF<\/jats:styled-content>\u20101 activity. Future studies will reveal how the modulation of angiopoietin\u2010like 4 in the periodontium contributes to periodontal disease and regeneration.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jre.12649","type":"journal-article","created":{"date-parts":[[2019,3,20]],"date-time":"2019-03-20T08:46:42Z","timestamp":1553071602000},"page":"489-498","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Angiopoietin\u2010like 4 production upon treatment with hypoxia and L\u2010mimosine in periodontal fibroblasts"],"prefix":"10.1111","volume":"54","author":[{"given":"Klara","family":"Janji\u0107","sequence":"first","affiliation":[{"name":"Department of Conservative Dentistry and Periodontology University Clinic of Dentistry Medical University of Vienna  Vienna Austria"},{"name":"Austrian Cluster for Tissue Regeneration  Vienna Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alwina","family":"Schellner","sequence":"additional","affiliation":[{"name":"Department of Conservative Dentistry and Periodontology University Clinic of Dentistry Medical University of Vienna  Vienna Austria"},{"name":"Austrian Cluster for Tissue Regeneration  Vienna Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Engenhart","sequence":"additional","affiliation":[{"name":"Department of Conservative Dentistry and Periodontology University Clinic of Dentistry Medical University of Vienna  Vienna Austria"},{"name":"Austrian Cluster for Tissue Regeneration  Vienna Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kurt","family":"Kernstock","sequence":"additional","affiliation":[{"name":"Department of Conservative Dentistry and Periodontology University Clinic of Dentistry Medical University of Vienna  Vienna Austria"},{"name":"Austrian Cluster for Tissue Regeneration  Vienna Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Sch\u00e4dl","sequence":"additional","affiliation":[{"name":"Austrian Cluster for Tissue Regeneration  Vienna Austria"},{"name":"Ludwig Boltzmann Institute for Experimental and Clinical Traumatology  Vienna Austria"},{"name":"University Clinic of Dentistry Medical University of Vienna  Vienna Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Moritz","sequence":"additional","affiliation":[{"name":"Department of Conservative Dentistry and Periodontology University Clinic of Dentistry Medical University of Vienna  Vienna Austria"},{"name":"Austrian Cluster for Tissue Regeneration  Vienna Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9509-1555","authenticated-orcid":false,"given":"Hermann","family":"Agis","sequence":"additional","affiliation":[{"name":"Department of Conservative Dentistry and Periodontology University Clinic of Dentistry Medical University of Vienna  Vienna Austria"},{"name":"Austrian Cluster for Tissue Regeneration  Vienna Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,3,20]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.4161\/org.25970"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2017.04.029"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcm.2007.10.003"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000250758.63358.91"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2014.102"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20110102"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.4805"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcms.2015.06.015"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.5051\/jpis.2011.41.1.30"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64285-X"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2017.00080"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.10.162230"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0109524"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2016.06.058"},{"key":"e_1_2_6_16_1","doi-asserted-by":"crossref","first-page":"54966","DOI":"10.18632\/oncotarget.18629","article-title":"TGF\u2010\u03b22\u2010induced ANGPTL4 expression promotes tumor progression and osteoclast differentiation in giant cell tumor of bone","volume":"8","author":"Li B","year":"2017","journal-title":"Oncotarget"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep44351"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0035-1554624"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-015-0152-2"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1590\/0103-6440201600533"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2010.100100"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10856-013-4908-3"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1177\/2472555217740576"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2010.100533"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2014.12.017"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034514550040"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2013.120703"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2015.08.002"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2012.08.003"},{"key":"e_1_2_6_30_1","first-page":"417","article-title":"Bone cell responsiveness to growth and differentiation factors under hypoxia in vitro","volume":"23","author":"Gruber R","year":"2008","journal-title":"Int J Oral Maxillofac Implants"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12903-017-0373-6"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2017.03.007"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/iej.12307"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.4070\/kcj.2014.44.3.177"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1177\/1534734614520704"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-013-0678-0"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2017.10.011"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-007-0301-8"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1677\/JOE-08-0156"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-1235"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M307583200"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.217638"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2016.5451"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2015.09.001"}],"container-title":["Journal of Periodontal Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjre.12649","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jre.12649","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jre.12649","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jre.12649","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T13:52:04Z","timestamp":1694267524000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jre.12649"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,20]]},"references-count":43,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2019,10]]}},"alternative-id":["10.1111\/jre.12649"],"URL":"https:\/\/doi.org\/10.1111\/jre.12649","archive":["Portico"],"relation":{},"ISSN":["0022-3484","1600-0765"],"issn-type":[{"value":"0022-3484","type":"print"},{"value":"1600-0765","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,20]]},"assertion":[{"value":"2018-03-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-02-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-03-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}