CD8+ T cell-induced expression of tissue inhibitor of metalloproteinses-1 exacerbated osteoarthritis

Int J Mol Sci. 2013 Oct 8;14(10):19951-70. doi: 10.3390/ijms141019951.

Abstract

Despites the fact that T cells are involved in the pathogenesis of osteoarthritis (OA) little is known about the roles of CD8+ T cells in this disease. We investigated the effects of CD8+ T cells and the expression of tissue inhibitor of metalloproteinases 1 (TIMP-1) on joint pathology. Using anterior cruciate ligament-transection (ACLT), OA was induced in mice. The knee joints were histologically assessed for manifestations of OA. The CD8+ T cells from splenocytes and synovium were flow-cytometrically and immunochemically evaluated, respectively. Local expression of TIMP-1, matrix metalloproteinase (MMP)-13, and VEGF were examined. Cartilage degeneration was slower in CD8+ T cell knockout mice than in control mice. CD8+ T cells were activated once OA was initiated and expanded during OA progression. More CD8+ T cells from splenocytes expressed TIMP-1 in ACLT-group mice than in Sham-group mice. The number of TIMP-1-expressing CD8+ T cells in OA mice correlated with the disease severity. TIMP-1 expression in cartilage was co-localized with that of MMP-13 and VEGF. TIMP-1 protein was detected in synovium in which angiogenesis occurred. During the pathogenesis of OA, the expression of TIMP-1, VEGF and MMP-13 accompanying with CD8+ T cells activation were increased. Furthermore, inhibiting the expression of TIMP-1 in joints could retard the progression of OA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anterior Cruciate Ligament / metabolism
  • Anterior Cruciate Ligament / pathology
  • CD8-Positive T-Lymphocytes / metabolism*
  • Cartilage / metabolism
  • Cartilage / pathology
  • Disease Progression
  • Knee Joint / metabolism
  • Knee Joint / pathology
  • Male
  • Matrix Metalloproteinase 13 / metabolism
  • Mice
  • Osteoarthritis / metabolism*
  • Osteoarthritis / pathology*
  • Synovial Membrane / metabolism
  • Synovial Membrane / pathology
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism*
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Timp1 protein, mouse
  • Tissue Inhibitor of Metalloproteinase-1
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, mouse
  • Matrix Metalloproteinase 13
  • Mmp13 protein, mouse