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Inhibitory Effect of Probenecid on Osteoclast Formation via JNK, ROS and COX-2

  • Cheng, Mi Hyun (Department of Pharmacology and Toxicology, School of Dentistry, Graduate School, Kyung Hee University) ;
  • Kim, Sung-Jin (Department of Pharmacology and Toxicology, School of Dentistry, Graduate School, Kyung Hee University)
  • Received : 2019.03.13
  • Accepted : 2019.08.09
  • Published : 2019.12.30

Abstract

Probenecid is a representative drug used in the treatment of gout. A recent study showed that probenecid effectively inhibits oxidative stress in neural cells. In the present study, we investigated whether probenecid can affect osteoclast formation through the inhibition of reactive oxygen species (ROS) formation in RAW264.7 cells. Lipopolysaccharide (LPS)-induced ROS levels were dose-dependently reduced by probenecid. Fluorescence microscopy analysis clearly showed that probenecid inhibits the generation of ROS. Western blot analysis indicated that probenecid affects two downstream signaling molecules of ROS, cyclooxygenase 2 (COX-2) and c-Jun N-terminal kinase (JNK). These results indicate that probenecid inhibits ROS generation and exerts antiosteoclastogenic activity by inhibiting the COX-2 and JNK pathways. These results suggest that probenecid could potentially be used as a therapeutic agent to prevent bone resorption.

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