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

FEBS Lett. 2015 May 22;589(12):1331-1339. doi: 10.1016/j.febslet.2015.04.008. Epub 2015 Apr 17.

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.

Keywords: Bone resorption; Cartilage destruction; Cathepsin K; Inflammation; Periodontitis; Rheumatoid arthritis; Toll-like receptors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / metabolism*
  • Arthritis, Rheumatoid / pathology
  • Arthritis, Rheumatoid / physiopathology
  • Bacteroidetes / growth & development
  • Bacteroidetes / immunology
  • Bone Resorption / etiology*
  • Cathepsin K / genetics
  • Cathepsin K / metabolism*
  • Crosses, Genetic
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Dendritic Cells / pathology
  • Female
  • Immunity, Innate*
  • Joint Capsule / immunology
  • Joint Capsule / metabolism
  • Joint Capsule / pathology
  • Macrophages / immunology
  • Macrophages / metabolism
  • Macrophages / pathology
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Osteochondritis / etiology*
  • Osteoclasts / immunology*
  • Periodontitis / immunology
  • Periodontitis / metabolism*
  • Periodontitis / microbiology
  • Periodontitis / physiopathology
  • Periodontium / immunology
  • Periodontium / metabolism
  • Periodontium / microbiology
  • Periodontium / pathology
  • Porphyromonas gingivalis / growth & development
  • Porphyromonas gingivalis / immunology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / pathology
  • Treponema denticola / growth & development
  • Treponema denticola / immunology
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • TNF protein, human
  • Tumor Necrosis Factor-alpha
  • Cathepsin K
  • Ctsk protein, mouse