Rebamipide, an Amino Acid Analog of 2(1H)‎-Quinolinone, Inhibits the Formation of Human Osteoclasts

Abstract EN

Objectives.

Drug repositioning or drug reprofiling (DR) has recently been growing in importance.

DR has a significant advantage over traditional drug development because the repositioned drug has already passed toxicity tests; its safety is known, and the risk of adverse toxicology is reduced.

In the current study, we investigated the role of rebamipide, a mucosa-protecting agent, with recently reported anti-inflammatory function, in human osteoclastogenesis.

Methods.

Peripheral blood mononuclear cells (PBMCs) were cultured in the presence of M-CSF and sRANKL.

Osteoclast formation was evaluated by immunohistological staining for CD51/61 (vitronectin receptors).

Osteoclast formation, in the presence or absence of rebamipide (0, 1, and 3 mM), was observed by time-lapse photography and actin ring formation.

The number of absorption sites and area of absorption were calculated using Osteologic™ plates.

Pit formation was studied by 3D-SEM.

Results.

Rebamipide inhibited human osteoclast formation at 3 mM, a pharmacological concentration, and inhibited resorbing activity dose-dependently.

Rebamipide induced the degradation of actin rings in mature osteoclasts.

This mechanism may involve inhibiting the osteoclast fusion pathway through reducing the expression of DC-specific transmembrane protein (DC-STAMP).

Conclusions.

The present study suggests that rebamipide would be useful as a novel agent for osteoporosis and rheumatoid arthritis.