{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T06:02:29Z","timestamp":1779948149330,"version":"3.53.1"},"reference-count":39,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T00:00:00Z","timestamp":1768694400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T00:00:00Z","timestamp":1768694400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Periodontal Research"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To investigate the contribution of the Single Immunoglobulin Interleukin\u20101 Receptor\u2010Related Molecule (SIGIRR), a recently described negative mediator of inflammation signaling, in experimental periodontitis pathogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A comprehensive approach was employed, including the analysis of human periodontal tissues, in\u00a0vitro experiments with Periodontal ligament stem cells (PDLSCs), and validation in a rat experimental periodontitis model. The mechanistic link between LPS stimulation and SIGIRR downregulation was investigated, focusing on the p38 pathway and transcription factor Sp1. Functional effects of SIGIRR overexpression on inflammatory cytokine production were assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>SIGIRR expression was markedly downregulated in periodontitis and LPS\u2010stimulated PDLSCs. This downregulation was mechanistically linked to LPS activation of the p38 pathway, which impaired nuclear translocation of the transcription factor Sp1, a key positive regulator of SIGIRR transcription. SIGIRR overexpression in PDLSCs significantly attenuated LPS\u2010induced production of pro\u2010inflammatory cytokines (IL\u20106, IL\u20108, TNF\u2010\u03b1). Local administration of a SIGIRR\u2010overexpressing lentivirus in the rat experimental periodontitis model effectively reduced local pro\u2010inflammatory cytokine levels, and promoted alveolar bone repair.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Together, our findings establish a unique role for p38\u2010Sp1\u2010SIGIRR axis in the pathogenesis of experimental periodontitis and provide evidence that SIGIRR gene therapy promises to offer an alternative option for inflammation blockade and bone repair, facilitating the development of a novel therapeutic strategy.<\/jats:p>\n                  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