Effects of Low-Dose Silver Nanoparticles on Odontoblastic Mineralization and Inflammatory Responses under an Inflammatory Microenvironment Subtitle: Involvement of the PI3K/Akt–NF-κB Signaling Pathway in MDPC-23 Cells

Silver nanoparticles (AgNPs) are extensively applied in biomedical fields due to their antimicrobial properties, but their regulatory effects on odontogenic cells under inflammatory conditions remain unclear. This work sought to analyze low-dose AgNP impact on mineralization and inflammatory responses in lipopolysaccharide (LPS)-stimulated MDPC-23 cells, and to assess the contribution of the PI3K/Akt-NF-κB pathway. MDPC-23 cells were exposed to 1 μg/mL LPS to simulate inflammation and then received 1 μg/mL AgNPs to assess their effects on cell viability, inflammation, and differentiation. To investigate pathway involvement, 10 μM PI3K agonist 740Y-P was introduced. CCK-8, qRT-PCR, ELISA, and immunoblotting were carried out, along with ALP activity and Alizarin Red S staining for assessing odontogenic function. AgNPs significantly restored cell viability (<i>P</i> < 0.001), upregulated DSPP, RUNX2, and ALP expression (<i>P</i> < 0.001), reduced TNF-α, IL-6, and IL-1β secretion (<i>P</i> < 0.001), and suppressed PI3K/Akt-NF-κB signaling activation (<i>P</i> < 0.001). Such changes were counteracted by 740Y-P. Low-dose AgNPs alleviate inflammation-induced impairment of odontogenic differentiation via modulation of the PI3K/Akt-NF-κB pathway.