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

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.

• Authors: Wenyu Feng, Jia Li, Shijie Liao, Shiting Ma, Feicui Li, Chaoyi Zhong, Guodong Li, Yan Wei, Huading Huang, Qingjun Wei, Jun Yao, Yun Liu
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 503 Issue 1 Pg. 62-70 (09 03 2018) ISSN: 1090-2104 [Electronic] United States
• PMID: 29856998 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• 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

Topics

• 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, metabolism, pathology)
• Osteoclasts (drug effects, metabolism, pathology)
• Osteogenesis (drug effects, genetics, physiology)
• Osteolysis (metabolism, pathology, prevention & control)
• Prosthesis Failure (adverse effects)
• Protein Kinase Inhibitors (pharmacology)
• RANK Ligand (metabolism)
• Skull (drug effects, metabolism, pathology)
• Titanium (adverse effects)
• p38 Mitogen-Activated Protein Kinases (metabolism)