Acidification induces OGR1/Ca2+/calpain signaling in gingival fibroblasts

Mi Seong Kim, Dong Min Shin, Min Seuk Kim

Research output: Contribution to journalArticle

Abstract

Gingivitis, the mildest form of periodontitis, is generally considered a consequence of prolonged exposure of the gingiva to periodontal pathogens. On the other hand, several epidemiologic reports have suggested that other etiologic factors such as oral acidification may also increase the susceptibility of the periodontium to destruction. However, the pathologic mechanism underlying the effects of oral acidification on the gingiva is still largely unknown. In this study, we analyzed molecular pathways mediating the influence of the acidic environment on human gingival fibroblasts (HGFs). Acidic extracellular pH caused biphasic increase of intracellular Ca2+ level ([Ca2+]i) through activation of ovarian cancer G protein-coupled receptor 1, phospholipase C, and Ca2+ release from the endoplasmic reticulum, but not through voltage-gated Ca2+ channels or extracellular Ca2+ influx via transient receptor potential cation channel subfamily V member 1. The acidic environment was also transiently cytotoxic for HGFs; however, the activation of pro-apoptotic proteins poly (ADP-ribose) polymerase-1 and BAX was not observed. Furthermore, we found that intracellular matrix metalloproteinase 1 was consistently upregulated in HGFs grown in regular medium, but significantly reduced in the acidic medium, which depended on [Ca2+]i increase, lysosomal pH homeostasis, and Ca2+-dependent protease calpain. Considering that HGFs, essential for oral wound healing, in the in vitro culture system are placed in wound repair-like conditions, our findings provide important insights into molecular mechanisms underlying HGF functional impairment and chronic damage to the gingiva caused by the acidic intraoral environment.

Original languageEnglish
Pages (from-to)693-699
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume496
Issue number2
DOIs
Publication statusPublished - 2018 Feb 5

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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