{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:48:49Z","timestamp":1786978129951,"version":"build-2736575974"},"reference-count":50,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2019,5,29]],"date-time":"2019-05-29T00:00:00Z","timestamp":1559088000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["P29440"],"award-info":[{"award-number":["P29440"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aap.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Periodontology"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Although periodontitis is associated with disruption of the host\u2010microbial homeostasis, viruses are currently discussed to influence disease progression. Viral pathogens are recognized by Toll\u2010like receptor (TLR)\u20103, which engages a different signaling pathway than other TLRs. This study aimed to investigate the effect of TLR\u20103 agonist polyinosinic:polycytidylic acid (Poly I:C) on the expression of inflammatory markers and bone metabolism proteins by human periodontal ligament stem cells (hPDLSCs) compared with TLR\u20102 agonist Pam3CSK4, which mimics the effect of bacterial lipoproteins. To assess potential combined effects of bacterial and viral infections, hPDLSCs response to simultaneous TLR\u20102 and TLR\u20103 activation was investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>HPDLSCs were stimulated with Poly I:C (0.0001\u20101\u00a0\u00b5g\/mL), Pam3CSK4 (1\u00a0\u00b5g\/mL), and their combinations for 24 hours. Gene expression and protein levels of interleukin (IL)\u20106, IL\u20108, monocyte chemoattractant protein (MCP)\u20101, and osteoprotegerin (OPG) were measured with qPCR and ELISA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Production of IL\u20106, IL\u20108, MCP\u20101, and OPG was significantly increased by Poly I:C or Pam3CSK4 to a similar extent. The levels of all inflammatory mediators induced by simultaneous stimulation with Poly I:C and Pam3CSK4 were significantly higher compared with single stimuli as well as to their summed response. Gene expression and protein levels of OPG were enhanced by Poly I:C, but by lesser extent than by Pam3CSK4. OPG levels upon simultaneous stimulation with Pam3CSK4 and Poly I:C were significantly lower compared with Pam3CSK4 stimulation alone.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Simultaneous TLR\u20102 and TLR\u20103 activation synergistically triggers IL\u20106, IL\u20108, and MCP\u20101 production, which was not observed for OPG. These findings suggest that TLR\u20103 activation by viral infections might promote periodontitis progression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jper.19-0005","type":"journal-article","created":{"date-parts":[[2019,5,3]],"date-time":"2019-05-03T01:59:42Z","timestamp":1556848782000},"page":"1190-1201","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Synergistic effects triggered by simultaneous Toll\u2010like receptor\u20102 and \u20103 activation in human periodontal ligament stem cells"],"prefix":"10.1002","volume":"90","author":[{"given":"Alice","family":"Blufstein","sequence":"first","affiliation":[{"name":"Department of Conservative Dentistry and Periodontology University Clinic of Dentistry Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Behm","sequence":"additional","affiliation":[{"name":"Department of 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