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Deficiency of cathepsin K prevents inflammation and bone erosion in rheumatoid arthritis and periodontitis and reveals its shared osteoimmune role
Author(s) -
Hao Liang,
Zhu Guochun,
Lu Yun,
Wang Min,
Jules Joel,
Zhou Xuedong,
Chen Wei
Publication year - 2015
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2015.04.008
Subject(s) - cathepsin k , inflammation , periodontitis , osteoimmunology , rheumatoid arthritis , immune system , osteoclast , bone erosion , immunology , proinflammatory cytokine , medicine , arthritis , cytokine , rankl , receptor , activator (genetics)
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.