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Tonsil‑derived mesenchymal stem cell‑derived extracellular vesicles suppress MAPK‑NF‑κB signaling and restore osteogenic differentiation in LPS‑stimulated periodontal ligament fibroblasts

Year: 2026
Type: article
Abstract: The present study evaluated and compared the anti-inflammatory and osteogenic effects of extracellular vesicles (EVs) derived from tonsil-derived mesenchymal stem cells (T-MSC-EVs) in a lipopolysaccharide (LPS)-induced in vitro model of periodontitis using human periodontal ligament fibroblasts (hPDLFs).hPDLFs were treated with LPS to induce inflammation, followed by treatment with T-MSC-EVs.Cell viability was assessed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.The expression levels of inflammatory cytokines (IL-1β, IL-6, IL-8 and IFN-γ) and osteogenic markers [alkaline phosphatase (ALP), bone sialoprotein, osteopontin, osteocalcin and sclerostin] were evaluated using reverse transcription-quantitative PCR.Inflammatory signaling proteins (phosphorylated ERK, phosphorylated JNK, c-Fos, c-Jun and NF-κB) were analyzed by western blotting.Osteogenic activity was assessed using an ALP activity assay and alizarin red staining over 21 days.Treatment with T-MSC-EVs significantly protected hPDLFs from LPS-induced growth suppression.T-MSC-EVs exhibited selective immunomodulation, reducing IL-8 and IFN-γ expression, while preserving IL-6 and IL-1β expression, which was accompanied by inhibited MAPK-activator protein 1 and NF-κB signaling.Finally, T-MSC-EVs restored the osteogenic potential by recovering ALP activity, mineral deposition and expression of osteogenic marker genes repressed by LPS.These findings underscore the therapeutic potential of EVs as next-generation biologics for periodontitis and emphasize the importance of selecting appropriate EV sources to achieve targeted immune modulation and tissue regeneration.
DOI: 10.3892/mmr.2026.13860
Language: English
Open Access status: hybrid
OpenAlex ID: W7140631775
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