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Biochem Biophys Res Commun ; 503(1): 62-70, 2018 09 03.
Article in English | MEDLINE | ID: mdl-29856998

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.


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