{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T13:52:12Z","timestamp":1789912332639,"version":"4.0.1"},"reference-count":37,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2019,5,1]],"date-time":"2019-05-01T00:00:00Z","timestamp":1556668800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2019,5,1]],"date-time":"2019-05-01T00:00:00Z","timestamp":1556668800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"name":"Grants-in-Aid for Scientific Research","award":["Young Scientists (B) \/ #17K17118"],"award-info":[{"award-number":["Young Scientists (B) \/ #17K17118"]}]},{"name":"Grants-in-Aid for Scientific Research","award":["Challenging Exploratory Research\/16K15795"],"award-info":[{"award-number":["Challenging Exploratory Research\/16K15795"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>microRNAs are small noncoding RNA molecules that regulate RNA silencing and posttranscriptional gene expression, and many microRNAs are involved in inflammatory processes. In particular, microRNA 21 (miR\u201021) is upregulated in inflammatory environment and reported to induce anti\u2010inflammatory responses. However, the involvement of miR\u201021 in pulpal inflammation and the precise mechanisms of anti\u2010inflammatory reactions induced by miR\u201021 remain unclear. We hypothesized that miR\u201021\u20105p expression is induced in lipopolysaccharide (LPS)\u2010stimulated human dental pulp cells (hDPCs) and that miR\u201021\u20105p downregulates the proinflammatory cytokine expression in LPS\u2010stimulated hDPCs. We found that miR\u201021\u20105p was upregulated in LPS\u2010stimulated hDPCs concomitant with elevated proinflammatory cytokine expression and nuclear factor\u2010kappa B (NF\u2010\u03baB) phosphorylation. miR\u201021\u20105p and cytokine expression were downregulated by BAY11\u20107085 and caffeic acid phenylethyl ester (CAPE), specific and potent NF\u2010\u03baB inhibitors. Enforced expression of miR\u201021\u20105p downregulated the Toll\u2010like receptor (TLR)\/NF\u2010\u03baB signaling via reducing the expression of TNF receptor\u2010associated factor 6 (TRAF6) and programmed cell death 4 (PDCD4), which further induced the decrease of proinflammatory cytokine expression. hDPCs forcibly overexpressing miR\u201021\u20105p downregulated the LPS\u2010induced expression of TNF receptor\u2010associated factor 6 (TRAF6; a component of the Toll\u2010like receptor [TLR]\/NF\u2010\u03baB signaling pathway), programmed cell death 4 (PDCD4, a positive regulator of the TLR\/NF\u2010\u03baB signaling pathway), and proinflammatory cytokines. In contrast, miR\u201021\u20105p inhibitor\u2010transfected hDPCs upregulated the expression of TRAF6, PDCD4, and inflammatory cytokines following LPS stimulation. These findings suggest that miR\u201021\u20105p expression was induced by the NF\u2010\u03baB signaling pathway, which was in turn negatively regulated by miR\u201021\u20105p via downregulation of TRAF6 and PDCD4 expression in LPS\u2010stimulated hDPCs.<\/jats:p>","DOI":"10.1002\/jcp.28737","type":"journal-article","created":{"date-parts":[[2019,5,1]],"date-time":"2019-05-01T06:55:01Z","timestamp":1556693701000},"page":"21331-21341","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Anti\u2010inflammatory roles of microRNA 21 in lipopolysaccharide\u2010stimulated human dental pulp cells"],"prefix":"10.1002","volume":"234","author":[{"given":"Keisuke","family":"Nara","sequence":"first","affiliation":[{"name":"Department of Pulp Biology and Endodontics Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU) Tokyo 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