title: Protection against ovariectomy-induced bone loss by tranilast.
abstract: BACKGROUND
  Tranilast (N-(3',4'-dimethoxycinnamonyl) anthranilic acid) has been shown to be therapeutically effective, exerting anti-inflammatory and anti-oxidative effects via acting on macrophage. We hypothesized that Tranilast may protect against oxidative stress-induced bone loss via action in osteoclasts (OCs) that shares precursors with macrophage.
  
  
  RESULTS
  To elucidate the role of Tranilast, ovariectomy (OVX)-induced bone loss in vivo and OC differentiation in vitro were evaluated by µCT and tartrate-resistant acid phosphatase staining, respectively. Oral administration of Tranilast protected against OVX-induced bone loss with decreased serum level of reactive oxygen species (ROS) in mice. Tranilast inhibited OC formation in vitro. Decreased osteoclastogenesis by Tranilast was due to a defect of receptor activator of nuclear factor-κB ligand (RANKL) signaling, at least partly via decreased activation of nuclear factor-κB and reduced induction and nuclear translocation of nuclear factor of activated T cells, cytoplasmic 1 (or NFAT2). Tranilast also decreased RANKL-induced a long lasting ROS level as well as TGF-β to inhibit osteoclastogenesis. Reduced ROS caused by Tranilast was due to the induction of ROS scavenging enzymes (peroxiredoxin 1, heme oxygenase-1, and glutathione peroxidase 1) as well as impaired ROS generation.
  
  
  CONCLUSIONS
  Our data suggests the therapeutic potential of Tranilast for amelioration of bone loss and oxidative stress due to loss of ovarian function.
authors.affiliation: Department of Biological Sciences, University of Ulsan, Ulsan, Korea.
authors.forename: Tien Van
authors.initials: TV
authors.lastname: Phan
authors.affiliation: Department of Biological Sciences, University of Ulsan, Ulsan, Korea.
authors.forename: Ke
authors.initials: K
authors.lastname: Ke
authors.affiliation: Department of Biological Sciences, University of Ulsan, Ulsan, Korea.
authors.forename: Ok-Joo
authors.initials: OJ
authors.lastname: Sul
authors.affiliation: Department of Biological Sciences, University of Ulsan, Ulsan, Korea.
authors.forename: Yun-Kyung
authors.initials: YK
authors.lastname: Park
authors.affiliation: Department of Dentistry, Seoul National University, Seoul, Korea.
authors.forename: Kack-Kyun
authors.initials: KK
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, University of Ulsan, Ulsan, Korea.
authors.forename: Yeon-Soo
authors.initials: YS
authors.lastname: Cho
authors.affiliation: Department of Biological Sciences, University of Ulsan, Ulsan, Korea.
authors.forename: Hun-Taeg
authors.initials: HT
authors.lastname: Chung
authors.affiliation: Department of Biological Sciences, University of Ulsan, Ulsan, Korea.
authors.forename: Hye-Seon
authors.initials: HS
authors.lastname: Choi
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000188:drug therapy* / Q000209:etiology*; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology; D005260:Female; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010052:Ovariectomy / Q000009:adverse effects*; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D053245:RANK Ligand / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D062367:ortho-Aminobenzoates / Q000627:therapeutic use*
chemical_list: D016328:NF-kappa B; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D020011:Protective Agents; D053245:RANK Ligand; D017382:Reactive Oxygen Species; D062367:ortho-Aminobenzoates; C012293:tranilast
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