title: Deficiency of cathepsin K prevents inflammation and bone erosion in rheumatoid arthritis and periodontitis and reveals its shared osteoimmune role.
abstract: Using rheumatoid arthritis (RA) and periodontitis mouse models, we demonstrate that RA and periodontitis share many pathological features, such as deregulated cytokine production, increased immune-cell infiltration, increased expression of Toll-like receptors (TLRs), and enhanced osteoclast activity and bone erosion. We reveal that genetic deletion of cathepsin K (Ctsk) caused a radical reduction in inflammation and bone erosion within RA joint capsules and periodontal lesions, a drastic decrease in immune-cell infiltration, and a significant reduction in osteoclasts, macrophages, dendritic and T-cells. Deficiency of Ctsk greatly decreased the expression of TLR-4, 5, and 9 and their downstream cytokines in periodontal gingival epithelial lesions and synovial RA lesions. Hence, Ctsk may be targeted to treat RA and periodontitis simultaneously due to its shared osteoimmune role.
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, SHEL 810, 1825 University Blvd, Birmingham, AL 35294-2182, United States of America.
authors.forename: Liang
authors.initials: L
authors.lastname: Hao
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, SHEL 810, 1825 University Blvd, Birmingham, AL 35294-2182, United States of America.
authors.forename: Guochun
authors.initials: G
authors.lastname: Zhu
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, SHEL 810, 1825 University Blvd, Birmingham, AL 35294-2182, United States of America.
authors.forename: Yun
authors.initials: Y
authors.lastname: Lu
authors.affiliation: The State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, Sichuan, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, SHEL 810, 1825 University Blvd, Birmingham, AL 35294-2182, United States of America.
authors.forename: Joel
authors.initials: J
authors.lastname: Jules
authors.affiliation: The State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, Sichuan, People's Republic of China.
authors.forename: Xuedong
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, SHEL 810, 1825 University Blvd, Birmingham, AL 35294-2182, United States of America.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D041963:Bacteroidetes / Q000254:growth & development / Q000276:immunology; D001862:Bone Resorption / Q000209:etiology*; D056657:Cathepsin K / Q000235:genetics / Q000378:metabolism*; D003433:Crosses, Genetic; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D007113:Immunity, Innate; D017746:Joint Capsule / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010007:Osteochondritis / Q000209:etiology*; D010010:Osteoclasts / Q000276:immunology*; D010518:Periodontitis / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000503:physiopathology; D010519:Periodontium / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D016966:Porphyromonas gingivalis / Q000254:growth & development / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D048373:Treponema denticola / Q000254:growth & development / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D056657:Cathepsin K; C534132:Ctsk protein, mouse
keywords: Bone resorption; Cartilage destruction; Cathepsin K; Inflammation; Periodontitis; Rheumatoid arthritis; Toll-like receptors