{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T09:55:07Z","timestamp":1791971707654,"version":"4.3.4"},"reference-count":53,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"vor","delay-in-days":286,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002873","name":"Chulalongkorn University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002873","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["International Journal of Dentistry"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>This study aimed to determine whether pseudouridine\u2010modified mRNA encoding vascular endothelial growth factor (VEGF) \u2010A induces VEGF production in human periodontal ligament cells (PDLCs), and to evaluate its effects on PDLC proliferation, osteogenic differentiation, and in vivo angiogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      PDLCs derived from healthy periodontal tissues were transfected with pseudouridine\u2010modified VEGF\u2010A mRNA using Lipofectamine 2000 (L2000) or treated with L2000 alone. VEGF secretion was quantified at 24\u201372\u2009h posttransfection. Cell viability and immune activation were also assessed. Supernatants collected at 48\u2009h were used to evaluate PDLC proliferation using the AlamarBlue assay. Osteogenic differentiation was assessed by Alizarin Red S staining and the expression of\n                      <jats:italic>alkaline phosphatase gene<\/jats:italic>\n                      (\n                      <jats:italic>ALPL<\/jats:italic>\n                      ),\n                      <jats:italic>RUNX2<\/jats:italic>\n                      , and\n                      <jats:italic>osteocalcin<\/jats:italic>\n                      (\n                      <jats:italic>OCN<\/jats:italic>\n                      ). Angiogenic activity was evaluated using the chorioallantoic membrane (CAM) assay in fertilized White Leghorn chicken eggs (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20097 per group). On embryonic day 8, filter papers loaded with supernatants from L2000\u2009+\u2009mRNA, L2000 groups, Dulbecco\u2019s phosphate\u2010buffered saline, or recombinant VEGF (rhVEGF) were placed on the CAM. After a 3\u2010day incubation, newly formed blood vessels were imaged and quantified.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      PDLCs transfected with pseudouridine\u2010modified VEGF\u2010A mRNA produced significantly higher VEGF levels than the control groups for up to 72\u2009h (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.05), without affecting cell viability or inducing innate immune activation. VEGF\u2010containing supernatants promoted PDLC proliferation. Direct VEGF mRNA transfection enhanced osteogenic differentiation and upregulated expression of osteogenic markers\n                      <jats:italic>ALPL<\/jats:italic>\n                      ,\n                      <jats:italic>RUNX2<\/jats:italic>\n                      , and\n                      <jats:italic>OCN<\/jats:italic>\n                      . In the CAM assay, abundant microvascular networks with a characteristic spoked\u2010wheel pattern were observed in both the VEGF mRNA and rhVEGF groups. Furthermore, the VEGF mRNA group showed a significantly greater increase in blood vessel formation than the control groups (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.01).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Pseudouridine\u2010modified VEGF\u2010A mRNA effectively induced VEGF production, which subsequently enhanced PDLC proliferation, osteogenesis, and in vivo angiogenesis. These findings support the potential of pseudouridine\u2010modified VEGF\u2010A mRNA as a promising therapeutic approach for periodontal regeneration.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/ijod\/8805818","type":"journal-article","created":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T09:35:19Z","timestamp":1791970519000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["In Vitro Cell Proliferation, Osteogenic Differentiation, and In Vivo Angiogenesis Induced by Modified mRNA Encoding Vascular Endothelial Growth Factor\u2010A"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5418-0092","authenticated-orcid":false,"given":"Noppadol","family":"Sa-Ard-Iam","sequence":"first","affiliation":[{"name":"Immunology Research Center Faculty of Dentistry Chulalongkorn University  Bangkok Thailand  chula.ac.th"},{"name":"Center of Excellence in Periodontal Disease and Dental Implant Chulalongkorn University  Bangkok Thailand  chula.ac.th"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9238-8122","authenticated-orcid":false,"given":"Mana","family":"Naratippakorn","sequence":"additional","affiliation":[{"name":"Department of Periodontology Faculty of Dentistry Chulalongkorn University  Bangkok Thailand  chula.ac.th"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2721-7229","authenticated-orcid":false,"given":"Chantrakorn","family":"Champaiboon","sequence":"additional","affiliation":[{"name":"Immunology Research Center Faculty of Dentistry Chulalongkorn University  Bangkok Thailand  chula.ac.th"},{"name":"Center of Excellence in Periodontal Disease and Dental Implant Chulalongkorn University  Bangkok Thailand  chula.ac.th"},{"name":"Department of Periodontology Faculty of Dentistry Chulalongkorn University  Bangkok Thailand  chula.ac.th"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,14]]},"reference":[{"key":"e_1_2_13_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2018.12.009"},{"key":"e_1_2_13_2_2","doi-asserted-by":"publisher","DOI":"10.1517\/14712598.2015.1057563"},{"key":"e_1_2_13_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4278"},{"key":"e_1_2_13_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.05.007"},{"key":"e_1_2_13_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2012.202"},{"key":"e_1_2_13_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2005.06.008"},{"key":"e_1_2_13_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2015.08.051"},{"key":"e_1_2_13_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2008.200"},{"key":"e_1_2_13_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1775"},{"key":"e_1_2_13_10_2","doi-asserted-by":"publisher","DOI":"10.1208\/aapsj0901003"},{"key":"e_1_2_13_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mt.6300101"},{"key":"e_1_2_13_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2015.08.007"},{"key":"e_1_2_13_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2012.7"},{"key":"e_1_2_13_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2016.46"},{"key":"e_1_2_13_15_2","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2018.0112"},{"key":"e_1_2_13_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0603-669"},{"key":"e_1_2_13_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63754-6"},{"key":"e_1_2_13_18_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1524-475X.2003.11208.x"},{"key":"e_1_2_13_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2017.02.009"},{"key":"e_1_2_13_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3301798"},{"key":"e_1_2_13_21_2","doi-asserted-by":"publisher","DOI":"10.1089\/wound.2013.0517"},{"key":"e_1_2_13_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.152324099"},{"key":"e_1_2_13_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000099243.20096.FA"},{"key":"e_1_2_13_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0757.2008.00287.x"},{"key":"e_1_2_13_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.13048"},{"key":"e_1_2_13_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2008.05.027"},{"key":"e_1_2_13_27_2","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2010.0555"},{"key":"e_1_2_13_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2682"},{"key":"e_1_2_13_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2018.04.003"},{"key":"e_1_2_13_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12516"},{"key":"e_1_2_13_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-08852-4"},{"key":"e_1_2_13_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2022.11.017"},{"key":"e_1_2_13_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-026-01459-7"},{"key":"e_1_2_13_34_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-014-9440-7"},{"key":"e_1_2_13_35_2","doi-asserted-by":"publisher","DOI":"10.3390\/biology10040301"},{"key":"e_1_2_13_36_2","unstructured":"NaratippakornM. ChampaiboonC. andSa-Ard-IamN. et al.Expression of Vascular Endothelial Growth Factor Protein in mRNA Transfected Human Periodontal Ligament Cells Proceedings of RSU International Research Conference 2022 Thailand Pathum Thani 226\u2013235."},{"key":"e_1_2_13_37_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.2010.01597.x"},{"key":"e_1_2_13_38_2","first-page":"77","article-title":"Isolation of Mononuclear Cells and Granulocytes From Human Blood: Isolation of Mononuclear Cells by One Centrifugation, and of Granulocytes by Combining Centrifugation and Sedimentation at 1\u2009g","volume":"97","author":"B\u00f6yum A.","year":"1968","journal-title":"Scandinavian Journal of Clinical and Laboratory Investigation Supplement"},{"key":"e_1_2_13_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-020-01606-9"},{"key":"e_1_2_13_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-99979-6"},{"key":"e_1_2_13_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-53249-4"},{"key":"e_1_2_13_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.13"},{"key":"e_1_2_13_43_2","doi-asserted-by":"publisher","DOI":"10.1387\/ijdb.103138dr"},{"key":"e_1_2_13_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpb.2008.09.016"},{"key":"e_1_2_13_45_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00216-010-3821-6"},{"key":"e_1_2_13_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10144"},{"key":"e_1_2_13_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2005.11.008"},{"key":"e_1_2_13_48_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-020-02008-8"},{"key":"e_1_2_13_49_2","doi-asserted-by":"publisher","DOI":"10.1067\/mcp.2002.126179"},{"key":"e_1_2_13_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2013.112"},{"key":"e_1_2_13_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)16627-0"},{"key":"e_1_2_13_52_2","doi-asserted-by":"publisher","DOI":"10.1002\/cbf.2911"},{"key":"e_1_2_13_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/9467"}],"container-title":["International Journal of Dentistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/ijod\/8805818","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1155\/ijod\/8805818","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/ijod\/8805818","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T09:35:21Z","timestamp":1791970521000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/ijod\/8805818"}},"subtitle":[],"editor":[{"given":"Hannah","family":"Wesley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":53,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1155\/ijod\/8805818"],"URL":"https:\/\/doi.org\/10.1155\/ijod\/8805818","archive":["Portico"],"relation":{},"ISSN":["1687-8728","1687-8736"],"issn-type":[{"value":"1687-8728","type":"print"},{"value":"1687-8736","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"2026-04-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"8805818"}}