Streptolysin O derived from Streptococcus pyogenes inhibits RANKL‑induced osteoclastogenesis through the NF‑κB signaling pathway

Mol Med Rep. 2019 Jan;19(1):414-422. doi: 10.3892/mmr.2018.9662. Epub 2018 Nov 15.

Abstract

Streptococcus pyogenes (GAS) is a clinically significant bacterial strain that causes bacterial arthritis, osteomyelitis and implant infections. Infection complications can lead to serious bone destruction. Osteoclasts, the only type of cell with bone resorption function, participate in this process. Streptolysin O (SLO) is produced by almost all clinical Streptococcus pyogenes isolates. However, the role of SLO in bone infection caused by GAS had not been previously examined. The current study was performed to define the effects of SLO on receptor activator of NF‑κB ligand‑stimulated osteoclast differentiation in vitro. Results demonstrated that SLO decreased the phosphorylation of p65 and NF‑κB inhibitor α, suppressed c‑FOS and nuclear factor of activated T‑cells cytoplasmic 1, and downregulated the expression of osteoclast marker genes. SLO also induced apoptosis of mature osteoclasts. The results suggested that SLO blocked osteoclast activation during GAS infection. These findings may prove useful in the development of novel strategies for treating GAS‑associated bone infectious diseases.

Keywords: GAS; SLO; bone infection; osteoclast; NF-κB.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Bacterial Proteins / pharmacology
  • Biomarkers / metabolism
  • Bone Resorption / drug therapy
  • Bone Resorption / metabolism
  • Cell Differentiation / drug effects
  • Cell Line
  • Down-Regulation / drug effects
  • Mice
  • NF-kappa B / metabolism*
  • Osteoclasts / drug effects*
  • Osteoclasts / metabolism
  • Osteogenesis / drug effects*
  • RANK Ligand / metabolism*
  • RAW 264.7 Cells
  • Signal Transduction / drug effects*
  • Streptococcus pyogenes / metabolism*
  • Streptolysins / pharmacology*

Substances

  • Bacterial Proteins
  • Biomarkers
  • NF-kappa B
  • RANK Ligand
  • Streptolysins
  • Tnfsf11 protein, mouse
  • streptolysin O