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Inflammation

, Volume 37, Issue 4, pp 995–1005 | Cite as

Tyrosine Kinase Inhibitor Tyrphostin AG490 Retards Chronic Joint Inflammation in Mice

  • Valeriya Gyurkovska
  • Tsvetanka Stefanova
  • Petya Dimitrova
  • Svetla Danova
  • Rositsa Tropcheva
  • Nina Ivanovska
Article

Abstract

Tyrphostin AG490 is a Janus kinase (JAK) 2 inhibitor that is clinically used as an anticancer agent and is also effective in various models of inflammatory and autoimmune diseases. In this study, we examined the effects of tyrphostin AG490 on the development of collagenase-induced osteoarthritis (CIOA). Our results showed that tyrphostin-ameliorated cartilage and bone destructions. This effect was associated with decreased expression of signal transducers and activators of transcription 3 (STAT3), phosphorylated JAK2, Dickkopf homolog 1, and receptor activator of nuclear factor κB ligand (RANKL) in the joints of arthritic mice. Tyrphostin AG490 suppressed STAT3 phosphorylation and the expression of tumor necrosis factor-related apoptosis-inducing ligand and RANKL by synovial fluid cells. The drug inhibited RANKL-induced osteoclast differentiation in vitro. Molecules, such as tyrphostin AG490 that limit bone erosion and influence osteoclast generation, might have therapeutic utility in joint degenerative disorders.

KEY WORDS

collagenase-induced osteoarthritis (CIOA) osteoclasts tyrphostin AG490 STAT3 TRAIL 

Notes

Acknowledgments

This work was supported by a Grant DFNI B01/6 from the National Science Fund, Ministry of Education and Science, Republic of Bulgaria.

Conflict of interest

None

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Valeriya Gyurkovska
    • 1
  • Tsvetanka Stefanova
    • 1
  • Petya Dimitrova
    • 1
  • Svetla Danova
    • 2
  • Rositsa Tropcheva
    • 2
  • Nina Ivanovska
    • 1
  1. 1.Department of ImmunologyInstitute of MicrobiologySofiaBulgaria
  2. 2.Section of Microbial GeneticsInstitute of MicrobiologySofiaBulgaria

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