Interleukin-38 promotes alveolar bone repair in periodontitis by suppressing the nuclear factor kappa B pathway
- 1Key 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
- 2School of Preclinical Medicine of Zunyi Medical University, Zunyi Medical University
- 3Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University
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.
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BibTeX
@article{han2026interleukin38,
title = {{Interleukin-38 promotes alveolar bone repair in periodontitis by suppressing the nuclear factor kappa B pathway}},
author = {Yalin Han and Xi Xu and Shan Zhao and Hui Wang and Shengmei Wei and Jia Xu and Yina Wang and Yuan Hu and Xinyue Li and Jiamin Ai and Guangping Lang and Yingying Han},
journal = {Stem Cell Research \& Therapy},
year = {2026},
month = jul,
doi = {10.1186/s13287-026-05146-7},
url = {https://doi.org/10.1186/s13287-026-05146-7},
note = {CC BY},
}
RIS
TY - JOUR
TI - Interleukin-38 promotes alveolar bone repair in periodontitis by suppressing the nuclear factor kappa B pathway
AU - Yalin Han
AU - Xi Xu
AU - Shan Zhao
AU - Hui Wang
AU - Shengmei Wei
AU - Jia Xu
AU - Yina Wang
AU - Yuan Hu
AU - Xinyue Li
AU - Jiamin Ai
AU - Guangping Lang
AU - Yingying Han
PY - 2026
DA - 2026/07/01
JO - Stem Cell Research & Therapy
DO - 10.1186/s13287-026-05146-7
UR - https://doi.org/10.1186/s13287-026-05146-7
AB - 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.
SN - 1757-6512
ER -