PMID- 34058723 OWN - NLM STAT- MEDLINE DCOM- 20210615 LR - 20210615 IS - 1879-1506 (Electronic) IS - 0003-9969 (Linking) VI - 128 DP - 2021 Aug TI - Gene expression profiles of mitochondria-endoplasmic reticulum tethering in human gingival fibroblasts in response to periodontal pathogens. PG - 105173 LID - S0003-9969(21)00136-9 [pii] LID - 10.1016/j.archoralbio.2021.105173 [doi] AB - OBJECTIVE: 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 glucose-regulated 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 mug/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. CI - Copyright (c) 2021 Elsevier Ltd. All rights reserved. FAU - Aral, Kubra AU - Aral K AD - School of Dentistry, University of Birmingham, Birmingham, UK; Department of Periodontology, Faculty of Dentistry, Inonu University, Malatya, Turkey. Electronic address: drkubraaral@gmail.com. FAU - Milward, Michael R AU - Milward MR AD - School of Dentistry, University of Birmingham, Birmingham, UK. FAU - Cooper, Paul R AU - Cooper PR AD - School of Dentistry, University of Birmingham, Birmingham, UK; Sir John Walsh Research Institute, Faculty of Dentistry, University of Otago, Dunedin, New Zealand. LA - eng PT - Journal Article DEP - 20210527 PL - England TA - Arch Oral Biol JT - Archives of oral biology JID - 0116711 SB - IM MH - Endoplasmic Reticulum MH - Fibroblasts MH - Fusobacterium nucleatum MH - *Gingiva MH - Humans MH - Mitochondria MH - Porphyromonas gingivalis MH - *Transcriptome OTO - NOTNLM OT - Endoplasmic reticulum OT - Fusobacterium nucleatum OT - Gingival fibroblasts OT - Mitochondria OT - Periodontal disease OT - Porphyromonas gingivalis EDAT- 2021/06/01 06:00 MHDA- 2021/06/16 06:00 CRDT- 2021/05/31 20:30 PHST- 2021/03/09 00:00 [received] PHST- 2021/05/21 00:00 [revised] PHST- 2021/05/24 00:00 [accepted] PHST- 2021/06/01 06:00 [pubmed] PHST- 2021/06/16 06:00 [medline] PHST- 2021/05/31 20:30 [entrez] AID - S0003-9969(21)00136-9 [pii] AID - 10.1016/j.archoralbio.2021.105173 [doi] PST - ppublish SO - Arch Oral Biol. 2021 Aug;128:105173. doi: 10.1016/j.archoralbio.2021.105173. Epub 2021 May 27.