title: Odanacatib, A Cathepsin K-Specific Inhibitor, Inhibits Inflammation and Bone Loss Caused by Periodontal Diseases.
abstract: BACKGROUND
  Periodontitis is a bacteria-induced inflammatory disease mainly affecting periodontal tissues, leading to periodontal inflammation, bone breakdown, and loss of the tooth. The main obstacle for treating periodontitis effectively is the difficulty in finding a target that can inhibit bone loss and inflammation simultaneously. Recent studies showed that cathepsin K (CTSK) might have functions in the immune system besides its role in osteoclasts. Thus, targeting CTSK would have a potential therapeutic effect in both the bone system and the immune system during the progression of periodontitis.
  
  
  METHODS
  In the current study, a small molecular inhibitor (odanacatib [ODN]) is explored to inhibit the function of CTSK in a bacteria-induced periodontitis mouse model.
  
  
  RESULTS
  The application of ODN decreased the number of osteoclasts, macrophages, and T cells, as well as the expression of Toll-like receptors (TLRs) in the periodontitis lesion area. Furthermore, lack of CTSK inhibited the expression of TLR4, TLR5, and TLR9 and their downstream cytokine signaling in the gingival epithelial cells in periodontitis lesions, demonstrating that the innate immune response was inhibited in periodontitis.
  
  
  CONCLUSIONS
  The present results show that inhibition of CTSK can prevent bone loss and the immune response during the progression of periodontitis, indicating that CTSK is a promising target for treating inflammatory diseases such as periodontitis by affecting both osteoclasts and the immune system.
authors: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL.
authors: Liang
authors: L
authors: Hao
authors: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL.
authors: Jianwei
authors: J
authors: Chen
authors: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL.
authors: Zheng
authors: Z
authors: Zhu
authors: Department of Periodontology, University of Alabama at Birmingham School of Dentistry, Birmingham, AL.
authors: Michael S
authors: MS
authors: Reddy
authors: Department of Medicine, University of Alabama at Birmingham.
authors: John D
authors: JD
authors: Mountz
authors: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL.|Department of Periodontology, University of Alabama at Birmingham School of Dentistry, Birmingham, AL.
authors: Wei
authors: W
authors: Chen
authors: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL.|Department of Periodontology, University of Alabama at Birmingham School of Dentistry, Birmingham, AL.
authors: Yi-Ping
authors: YP
authors: Li
mesh_terms: D016301:Alveolar Bone Loss / Q000382:microbiology / Q000517:prevention & control*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D016866:Bacteroidaceae Infections / Q000276:immunology; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D056657:Cathepsin K / Q000037:antagonists & inhibitors*; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects; D005260:Female; D005881:Gingiva / Q000187:drug effects; D016905:Gram-Negative Bacterial Infections / Q000276:immunology; D007113:Immunity, Innate / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D010010:Osteoclasts / Q000187:drug effects; D010518:Periodontitis / Q000382:microbiology / Q000517:prevention & control*; D016966:Porphyromonas gingivalis / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects; D000070436:Tannerella forsythia / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors; D051198:Toll-Like Receptor 5 / Q000037:antagonists & inhibitors; D051217:Toll-Like Receptor 9 / Q000037:antagonists & inhibitors; D048373:Treponema denticola / Q000276:immunology; D014211:Treponemal Infections / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D001713:Biphenyl Compounds; C493487:Tlr4 protein, mouse; C495370:Tlr9 protein, mouse; D051197:Toll-Like Receptor 4; D051198:Toll-Like Receptor 5; D051217:Toll-Like Receptor 9; D056657:Cathepsin K; C534132:Ctsk protein, mouse; C527128:odanacatib
keywords: Bone resorption; Toll-like receptors; cathepsin K; macrophages; osteoclasts; periodontal diseases