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Res."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Periodontitis (PD) is characterized by localized inflammatory tissue destruction, yet the lesion-associated microRNA (miRNA)networks that regulate host immune responses remain incompletely defined. In this study, we aimed to identify and characterize dysregulated gingivalmiRNAs in PD that modulate inflammatory responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using a split-mouth design, miRNA expression was profiled in gingival biopsies fromperiodontal lesions and clinically healthy sites. Differentially expressed miRNAs were identified by microarray analysis, and selected candidates werevalidated by RT-qPCR. The responses of candidate miRNAs to periodontal bacterial challenge were evaluated, followed by functional studies ofmacrophage polarization, phagocytosis, inflammatory cytokine production, and target-gene regulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Microarray analysis identified 48differentially expressed miRNAs, including several upregulated non-canonical miRNAs. Among these, the Dicer-independent miRNAs miR-451a andmiR-1228 showed dose- and time-dependent induction following periodontal bacterial challenge. miR-451a, but not miR-1228, promoted a pro-inflammatory M1-like macrophage phenotype, characterized by increased HLA-DR and CD32 and reduced CD206 and CD163 expression. miR-451adirectly targeted multiple genes associated with M2 macrophage polarization, and its expression in inflamed gingival tissues inversely correlated with M2markers. miR-451a overexpression also reduced macrophage phagocytosis of E. coli and P. gingivalis while increasing pro-inflammatory cytokineproduction. Mechanistically, miR-451a directly suppressed SOCS3 and SOCS5, key negative regulators of JAK\/STAT signaling, in TLR4-stimulated cells.The antagonistic expression patterns of miR-451a, SOCS3, and SOCS5 in PD further supported the functional relevance of this regulatory axis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>miR-451a is a pathogen-responsive, PD-associated miRNA that promotes pro-inflammatory macrophage polarization, impairs bacterialphagocytosis, and amplifies inflammation through suppression of SOCS-mediated immune regulation. These findings identify the miR-451a\u2013SOCS3\/SOCS5 axis as a potential mechanism linking bacterial challenge to dysregulated macrophage responses in PD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00011-026-02381-9","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T18:07:13Z","timestamp":1791310033000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dicer-independent miR-451a is upregulated in periodontitis and potentiates inflammation by impairing macrophage polarization and SOCS activity"],"prefix":"10.1007","volume":"75","author":[{"given":"Raza Ali","family":"Naqvi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Maddalozzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kreena","family":"Amin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristelle","family":"Capistrano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Araceli","family":"Valverde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rani","family":"Rahat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasan","family":"Siddiqui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine D.","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoping","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Pettiette","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Moretti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gatikrushna","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvador","family":"Nares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7436-3056","authenticated-orcid":false,"given":"Afsar","family":"Naqvi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"issue":"1","key":"2381_CR1","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1111\/j.1600-0757.2011.00413.x","volume":"58","author":"BA Dye","year":"2012","unstructured":"Dye BA. 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