Oxidative stress induced pyroptosis leads to osteogenic dysfunction of MG63 cells

J Mol Histol. 2020 Jun;51(3):221-232. doi: 10.1007/s10735-020-09874-9. Epub 2020 Apr 30.

Abstract

Periodontitis is characterized by alveolar bone destruction and is one of the most common chronic oral diseases. Inflammatory cytokines released by pyroptosis, which can be triggered by oxidative stress, are critical in the development of periodontitis. This study aims to clarify whether oxidative stress causes osteoblast dysfunction by inducing pyroptosis in the process of periodontitis. We found that treatment with lipopolysaccharide (LPS) led to NLRP3 inflammasome-mediated pyroptosis of MG63 cells as well as decreased cell migration. Of note, LPS stimulation increased LDH release in a time- and dose-dependent manner. However, inhibition of reactive oxygen species with N-acetyl-L-cysteine attenuated oxidative stress-mediated pyroptosis and improved migration injury in osteoblasts treated with LPS. Further, inhibition of the NLRP3 inflammasome with MCC950 improved osteoblast migration and restored the expression of osteogenic differentiation-related proteins such as COL 1, RUNX 2 and ALP. In conclusion, oxidative stress caused by LPS induces pyroptosis in osteoblasts, leading to osteogenic dysfunction.

Keywords: Migration; Mineralization; Osteoblast; Oxidative stress; Periodontitis; Pyroptosis.

MeSH terms

  • Antioxidants / metabolism
  • Cell Line
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Humans
  • Inflammasomes / metabolism*
  • Lipopolysaccharides / pharmacology
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Osteoblasts / drug effects*
  • Osteoblasts / immunology
  • Osteoblasts / metabolism
  • Osteoblasts / pathology
  • Osteogenesis / drug effects*
  • Osteogenesis / immunology
  • Oxidative Stress / drug effects*
  • Oxidative Stress / immunology
  • Periodontitis / immunology
  • Periodontitis / metabolism*
  • Periodontitis / pathology
  • Pyroptosis / drug effects*
  • Pyroptosis / immunology
  • Reactive Oxygen Species / metabolism

Substances

  • Antioxidants
  • Inflammasomes
  • Lipopolysaccharides
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • Reactive Oxygen Species