Cepharanthine ameliorates titanium particle-induced osteolysis by inhibiting osteoclastogenesis and modulating OPG/RANKL ratio in a murine model

Biochem Biophys Res Commun. 2019 Sep 24;517(3):407-412. doi: 10.1016/j.bbrc.2019.07.115. Epub 2019 Aug 1.

Abstract

Periprosthetic asepteic loosening, caused by wear debris, is one of the most severe complications, generally resulting in implant failure. Extensive osteoclast formation and activation are considered as the cause for periprosthetic osteolysis. However, few approaches have been approved to be used for preventing early-stage periprosthetic osteolysis. In this study, we investigated the preventive effects of CEP on titanium particles-induced osteolysis in a murine calvaria model. This inhibitory effect was confirmed to be realized by attenuating osteoclastogenesis in vivo. In addition, CEP markedly reduced wear particles-induced elevation of receptor activator of nuclear factor kappa B ligand (RANKL)/Osteoprotegerin (OPG) ratio in vivo. In conclusion, these data concluded that CEP demonstrated a preventive effect of CEP on titanium particles induced osteolysis, suggesting that CEP might be a novel therapeutic for periprosthesis loosening.

Keywords: Cepharanthine; OPG; Osteoclast; Osteolysis; RANKL.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Benzylisoquinolines / pharmacology*
  • Bone-Anchored Prosthesis
  • Bone-Implant Interface / surgery
  • Cathepsin D / genetics
  • Cathepsin D / metabolism
  • Disease Models, Animal
  • Gene Expression Regulation
  • Male
  • Mice
  • NFATC Transcription Factors / genetics
  • NFATC Transcription Factors / metabolism
  • Osteoclasts / drug effects*
  • Osteoclasts / metabolism
  • Osteoclasts / pathology
  • Osteogenesis / drug effects*
  • Osteogenesis / genetics
  • Osteolysis / chemically induced
  • Osteolysis / genetics
  • Osteolysis / pathology
  • Osteolysis / prevention & control*
  • Osteoprotegerin / antagonists & inhibitors
  • Osteoprotegerin / genetics*
  • Osteoprotegerin / metabolism
  • Prosthesis Failure / drug effects
  • RANK Ligand / antagonists & inhibitors
  • RANK Ligand / genetics*
  • RANK Ligand / metabolism
  • Skull / drug effects
  • Skull / surgery
  • Tartrate-Resistant Acid Phosphatase / genetics
  • Tartrate-Resistant Acid Phosphatase / metabolism
  • Titanium / adverse effects*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Benzylisoquinolines
  • NFATC Transcription Factors
  • Nfatc1 protein, mouse
  • Osteoprotegerin
  • RANK Ligand
  • Tnfrsf11b protein, mouse
  • Tnfsf11 protein, mouse
  • cepharanthine
  • Titanium
  • Acp5 protein, mouse
  • Tartrate-Resistant Acid Phosphatase
  • Cathepsin D
  • Ctsd protein, mouse