Deficiency of cathepsin K prevents inflammation and bone erosion in rheumatoid arthritis and periodontitis and reveals its shared osteoimmune role

被引：81

作者：

Hao, Liang ^{[1
]}

Zhu, Guochun ^{[1
]}

Lu, Yun ^{[1
]}

Wang, Min ^{[2
]}

Jules, Joel ^{[1
]}

Zhou, Xuedong ^{[2
]}

Chen, Wei ^{[1
]}

机构：

[1] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA

[2] Sichuan Univ, West China Coll Stomatol, State Key Lab Oral Dis, Chengdu, Sichuan, Peoples R China

来源：

FEBS LETTERS | 2015年 / 589卷 / 12期

关键词：

Periodontitis; Rheumatoid arthritis; Toll-like receptors; Cathepsin K; Bone resorption; Cartilage destruction; Inflammation; TOLL-LIKE RECEPTORS; PORPHYROMONAS-GINGIVALIS; IMMUNE-RESPONSE; ASSOCIATION; RESORPTION; DISEASE; CELLS; DESTRUCTION; EXPRESSION; INFECTION;

D O I：

10.1016/j.febslet.2015.04.008

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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.

引用

页码：1331 / 1339

页数：9

共 41 条

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