Gö6983 attenuates titanium particle-induced osteolysis and RANKL mediated osteoclastogenesis through the suppression of NFκB/JNK/p38 pathways

Biochem Biophys Res Commun. 2018 Sep 3;503(1):62-70. doi: 10.1016/j.bbrc.2018.05.177. Epub 2018 Jun 6.

Abstract

Osteoclast activation by wear particles has caused major difficulties for surgeons. Wear particles are the main causes of aseptic prosthetic loosening. Gö6983, a protein kinase C inhibitor, inhibits five subtypes of protein kinase C family members. Here, we found that Gö6983 had an obviously inhibitory effect on wear-particles-induced osteolysis in vivo. In vitro, Gö6983 inhibited RANKL-stimulated osteoclast formation and function by inhibiting the RANKL-stimulated nuclear factor-κB/JNK/p38 signaling pathway. We also observed that Go6983 had no effect on the differentiation of osteoblasts and osteoblast-associated genes expression. According to our data, Gö6983 has potential therapeutic effects for aseptic prosthetic loosening caused by osteoclast activation.

Keywords: Gö6983; Osteoclast; RANKL; Titanium particle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Disease Models, Animal
  • Down-Regulation / drug effects
  • Durapatite / metabolism
  • Humans
  • In Vitro Techniques
  • Indoles / pharmacology*
  • MAP Kinase Signaling System / drug effects
  • Male
  • Maleimides / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism
  • Osteoblasts / pathology
  • Osteoclasts / drug effects
  • Osteoclasts / metabolism
  • Osteoclasts / pathology
  • Osteogenesis / drug effects*
  • Osteogenesis / genetics
  • Osteogenesis / physiology
  • Osteolysis / metabolism
  • Osteolysis / pathology
  • Osteolysis / prevention & control*
  • Prosthesis Failure / adverse effects
  • Protein Kinase Inhibitors / pharmacology
  • RANK Ligand / metabolism*
  • Skull / drug effects
  • Skull / metabolism
  • Skull / pathology
  • Titanium / adverse effects*
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • 2-(1-(3-dimethylaminopropyl)-5-methoxyindol-3-yl)-3-(1H-indol-3-yl)maleimide
  • Indoles
  • Maleimides
  • NF-kappa B
  • Protein Kinase Inhibitors
  • RANK Ligand
  • Tnfsf11 protein, mouse
  • Durapatite
  • Titanium
  • p38 Mitogen-Activated Protein Kinases