AIMS: Oxidized low-density lipoprotein (oxLDL) is an important player in the course of metabolic inflammatory diseases. oxLDL was identified in the gingival crevicular fluid, denoting possible associations between oxLDL-induced inflammation and periodontal disease. The current investigation compared for the first-time direct effects of oxLDL to a cytokine cocktail of IL-1ß/TNF-ɑ/INF-γ on gingival mesenchymal stem cells' (G-MSCs) attributes. METHODS: Human third passage G-MSCs, isolated from connective tissue biopsies (n = 5) and characterized, were stimulated in three groups over 7 days: control group, cytokine group (IL-1β[1 ng/mL], TNF-α[10 ng/mL], IFN-γ[100 ng/mL]), or oxLDL group (oxLDL [50 μg/mL]). Next Generation Sequencing and KEGG pathway enrichment analysis, stemness gene expression (NANOG/SOX2/OCT4A), cellular proliferation, colony-formation, multilinear potential, and altered intracellular pathways were investigated via histochemistry, next-generation sequencing, and RT-qPCR. RESULTS: G-MSCs exhibited all mesenchymal stem cells' characteristics. oxLDL group and cytokine group displayed no disparities in their stemness markers (p >
.05). Next-generation-sequencing revealed altered expression of the TXNIP gene in response to oxLDL treatment compared with controls (p = .04). Following an initial boosting for up to 5 days by inflammatory stimuli, over 14 day, cellular counts [median count ×10 CONCLUSIONS: Within the current investigation's limitations, in contrast to cytokine-mediated inflammation, G-MSCs appear to be minimally responsive to oxLDL-mediated metabolic inflammation, with little negative effect on their differentiation attributes and significantly reduced cellular proliferation.