title: Rebamipide, an Amino Acid Analog of 2(1H)-Quinolinone, Inhibits the Formation of Human Osteoclasts.
abstract: 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.
authors.affiliation: Institute of Rheumatology, Tokyo Women's Medical University, 10-22 Kawada-cho, Shinjuku-ku, Tokyo 162-0054, Japan.
authors.forename: Yuki
authors.identifier: 0000-0001-6269-0703
authors.initials: Y
authors.lastname: Nanke
authors.affiliation: Institute of Rheumatology, Tokyo Women's Medical University, 10-22 Kawada-cho, Shinjuku-ku, Tokyo 162-0054, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Kobashigawa
authors.affiliation: Institute of Rheumatology, Tokyo Women's Medical University, 10-22 Kawada-cho, Shinjuku-ku, Tokyo 162-0054, Japan.
authors.forename: Toru
authors.identifier: 0000-0003-1393-8615
authors.initials: T
authors.lastname: Yago
authors.affiliation: Institute of Rheumatology, Tokyo Women's Medical University, 10-22 Kawada-cho, Shinjuku-ku, Tokyo 162-0054, Japan.
authors.forename: Manabu
authors.identifier: 0000-0001-9442-6149
authors.initials: M
authors.lastname: Kawamoto
authors.affiliation: Institute of Rheumatology, Tokyo Women's Medical University, 10-22 Kawada-cho, Shinjuku-ku, Tokyo 162-0054, Japan.
authors.forename: Hisashi
authors.identifier: 0000-0001-8453-6731
authors.initials: H
authors.lastname: Yamanaka
authors.affiliation: Institute of Rheumatology, Tokyo Women's Medical University, 10-22 Kawada-cho, Shinjuku-ku, Tokyo 162-0054, Japan.
authors.forename: Shigeru
authors.identifier: 0000-0002-8922-0282
authors.initials: S
authors.lastname: Kotake
mesh_terms: D000409:Alanine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000700:Analgesics / Q000008:administration & dosage; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006873:Hydroquinones / Q000008:administration & dosage; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D015363:Quinolones / Q000008:administration & dosage*
chemical_list: D000700:Analgesics; D006873:Hydroquinones; D015363:Quinolones; C000594238:3,4-dihydro-2(1H)-quinolinone; C052785:rebamipide; D000409:Alanine