{ "abstract": "Background Periodontitis, characterized by chronic inflammation and alveolar bone loss, poses significant challenges to oral health. Interleukin-38 (IL-38) has emerged as a potential therapeutic agent due to its anti-inflammatory properties. This study aimed to investigate whether and how IL-38 protects against periodontitis in a ligation-induced periodontitis (LIP) mouse model and an inflammatory osteogenic model using human periodontal ligament stem cells (hPDLSCs). Methods 40 mice were divided into 4 groups (n = 10/group): Control, LIP, LIP + phosphate-buffered saline (PBS), LIP + IL-38. The animals were euthanized and tissue samples (jaws and gingivae) were collected on day 5. Recombinant mouse IL-38 (rmIL-38) lentivirus was used for IL-38 overexpression or knockdown in hPDLSCs in vitro, and shIL-38 hPDLSCs were ultimately treated with the NF-κB inhibitor Bay11-7082. The above tissue and cellular samples were collected for micro-computed tomography (micro-CT) imaging, histological, polymerase chain reaction (qRT-PCR) and Western blot (WB) to analyze bone microstructure, inflammatory markers, osteogenic markers, and the relevant protein level of the nuclear factor kappa B (NF-κB) pathway. Correction version for Methods: Forty mice were randomized into four groups (n = 10 per group): Control, ligature-induced periodontitis (LIP), LIP + PBS, and LIP + recombinant mouse IL-38 (rmIL-38). The LIP + rmIL-38 group received daily gingival rmIL-38 injection, and all mice were euthanized on day 5 to harvest jaw and gingival tissues. In vitro, lentiviral transfection generated IL-38-overexpressing and IL-38-knockdown hPDLSCs; NF-κB inhibitor Bay11-7082 was applied to IL-38-knockdown hPDLSCs for rescue assays. All tissue and cell samples were analyzed via micro-computed tomography (micro-CT) imaging, histological, polymerase chain reaction (qRT-PCR) and Western blot (WB) to analyze bone microstructure, inflammatory markers, osteogenic markers, and the relevant protein level of the nuclear factor kappa B (NF-κB) pathway. Results In vivo, rmIL-38 administration significantly reduced pro-inflammatory cytokine expression (Il1b, Il17a, Il6 and Il23a) and suppressed NF-κB pathway activation, which can be evidenced by decreased phospho-p65 levels. Furthermore, micro-CT analysis showed that rmIL-38 mitigated alveolar bone loss and improved the bone microstructure assessed. In vitro, IL-38 overexpression enhanced osteogenic marker expression (ALP, RUNX2, and COL1A1) while inhibiting NF-κB signaling, whereas IL-38 knockdown produced the opposite effects. Notably, Bay11-7082 treatment rescued impaired osteogenic marker expression in IL-38 knockdown hPDLSCs. Correction version for Results: In vivo, local rmIL-38 administration markedly suppressed pro-inflammatory cytokines Il17a and Il23a and upregulated the anti-inflammatory cytokine Il10. Micro-CT, immunofluorescence and Masson staining further confirmed that rmIL-38 alleviated alveolar bone loss and exerted pro-osteogenic effects. In vitro, IL-38 overexpression elevated osteogenic markers (ALP, RUNX2, COL1A1) and repressed NF-κB signaling, whereas IL-38 knockdown exerted opposite effects. Notably, NF-κB inhibition by Bay11-7082 rescued the impaired osteogenic capacity of IL-38-knockdown hPDLSCs. Conclusion Collectively, these findings suggest that IL-38 mitigates periodontitis progression by limiting inflammation and promoting osteogenic differentiation through NF-κB pathway inhibition, highlighting its potential as a therapeutic target in periodontal disease management.", "abstract_shown": true, "affiliations": [ "Key Laboratory of Oral Disease Research of The Education Department of Guizhou Province/Zunyi Laboratory of Oral Disease Research, School/Hospital of Stomatology, Zunyi Medical University", "School of Preclinical Medicine of Zunyi Medical University, Zunyi Medical University", "Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University" ], "article_type": null, "arxiv": null, "author_total": 12, "authors": [ { "affs": [ 0 ], "name": "Yalin Han" }, { "affs": [ 0 ], "name": "Xi Xu" }, { "affs": [ 0 ], "name": "Shan Zhao" }, { "affs": [ 0 ], "name": "Hui Wang" }, { "affs": [ 1 ], "name": "Shengmei Wei" }, { "affs": [ 1 ], "name": "Jia Xu" }, { "affs": [ 0 ], "name": "Yina Wang" }, { "affs": [ 2 ], "name": "Yuan Hu" }, { "affs": [ 2 ], "name": "Xinyue Li" }, { "affs": [ 2 ], "name": "Jiamin Ai" }, { "affs": [ 2 ], "name": "Guangping Lang" }, { "affs": [ 0 ], "name": "Yingying Han" } ], "bibtex": "https://research.draconitic.com/paper/as886arzfkphd.bib", "cited_by": 0, "doi": "10.1186/s13287-026-05146-7", "fulltext_url": "https://doi.org/10.1186/s13287-026-05146-7", "id": "as886arzfkphd", "issns": [ "1757-6512" ], "landing_url": "https://doi.org/10.1186/s13287-026-05146-7", "language": "en", "licence": "CC-BY", "licence_label": "CC BY", "licence_source": "journal", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "lcc", "QD415-436" ], [ "lcc", "R5-920" ], [ "openalex", "3506|Oral microbiology and periodontitis research" ] ], "openalex": "W7167632952", "pdf_url": null, "pmcid": null, "pmid": null, "published": "2026-07-01", "publisher": "BMC", "ris": "https://research.draconitic.com/paper/as886arzfkphd.ris", "sources": [ { "first_seen": "2026-10-30T13:45:46Z", "native_id": "9ae9d173859141a5ba417e9ba7bf9e68", "source": "doaj", "url": "https://doi.org/10.1186/s13287-026-05146-7" } ], "subjects": [ { "field": "biochemistry", "origin": "lcc:QD415-436", "subfield": "general" }, { "field": "medicine", "origin": "lcc:R5-920", "subfield": "general" } ], "title": "Interleukin-38 promotes alveolar bone repair in periodontitis by suppressing the nuclear factor kappa B pathway", "title_text": "Interleukin-38 promotes alveolar bone repair in periodontitis by suppressing the nuclear factor kappa B pathway", "type": "peer-reviewed", "updated_at": "2026-10-30T13:45:46Z", "url": "https://research.draconitic.com/paper/as886arzfkphd", "venue": "Stem Cell Research & Therapy", "versions": [] }