Aral, KubraMilward, Michael R.Cooper, Paul R.2024-08-042024-08-0420210003-99691879-1506https://doi.org/10.1016/j.archoralbio.2021.105173https://hdl.handle.net/11616/99965Objective: The current study aimed to elucidate the potential involvement of mitochondria-endoplasmic reticulum contact genes in the pathogenesis of periodontal disease by monitoring levels of contact associated genes including Mitofusion 1 (MFN1) and MFN2, inositol 1,4,5-trisphosphate receptor (IP3R), chaperone glucoseregulated protein 75 (GRP75), sigma non-opioid intracellular receptor 1 (SIGMAR1) and phosphate and tensin homolog induced putative kinase 1 (PINK1) in human gingival fibroblasts in response to periodontal pathogens Fusobacterium nucleatum (F. nucleatum) and Porphyromonas gingivalis (P. gingivalis) in vitro. Design: Primary human gingival fibroblasts were exposed to live cultures of P. gingivalis (W83; ATCC BAA-308) and F. nucleatum (subsp. Polymorphum; ATCC 10953) alone or in combination for 4 h at a 50 or 200 multiplicity of infection. Escherichia coli lipopolysaccharide (10 mu g/mL) exposure was used as a positive control. Gene expression levels of contact genes (MFN1, MFN2, IP3R, GRP75, SIGMAR1 and PINK1) as well as a proinflammatory cytokine, Tumor necrosis factor-alpha (TNF-alpha), and the apoptosis associated gene, Immediate early response 3 (IER3), were evaluated by reverse transcription polymerase chain reaction analysis. Results: MFN1, GRP75, IP3R and PINK1 were significantly upregulated by P. gingivalis with or without F. nucleatum. Only P. gingivalis with F. nucleatum caused a significant upregulation of SIGMAR1. TNF-alpha and IER3 gene expression positively correlated with the contact-associated gene expression changes. Conclusion: F. nucleatum and P. gingivalis alone or in combination may differentially dysregulate the gene expression levels of contact-associated genes in human gingival fibroblasts. These host-microbiome interactions may mechanistically be important in the pathogenesis of periodontal disease.eninfo:eu-repo/semantics/openAccessPeriodontal diseaseEndoplasmic reticulumPorphyromonas gingivalisFusobacterium nucleatumMitochondriaGingival fibroblastsArticle1283405872310.1016/j.archoralbio.2021.1051732-s2.0-85107114841Q2WOS:000659789300010Q3