期刊
FEBS LETTERS
卷 589, 期 12, 页码 1331-1339出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.febslet.2015.04.008
关键词
Periodontitis; Rheumatoid arthritis; Toll-like receptors; Cathepsin K; Bone resorption; Cartilage destruction; Inflammation
资金
- NIH [NIAMS. R01-AR-044741, NIDCR. R01DE023813]
- UAB Department of Pathology Start-Up funding
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. (C) 2015 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.
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