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01.08.2014

Tyrosine Kinase Inhibitor Tyrphostin AG490 Retards Chronic Joint Inflammation in Mice

verfasst von: Valeriya Gyurkovska, Tsvetanka Stefanova, Petya Dimitrova, Svetla Danova, Rositsa Tropcheva, Nina Ivanovska

Erschienen in: Inflammation | Ausgabe 4/2014

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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.

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Titel: Tyrosine Kinase Inhibitor Tyrphostin AG490 Retards Chronic Joint Inflammation in Mice
verfasst von: Valeriya Gyurkovska
Tsvetanka Stefanova
Petya Dimitrova
Svetla Danova
Rositsa Tropcheva
Nina Ivanovska
Publikationsdatum: 01.08.2014
Verlag: Springer US
Erschienen in: Inflammation / Ausgabe 4/2014
Print ISSN: 0360-3997
Elektronische ISSN: 1573-2576
DOI: https://doi.org/10.1007/s10753-014-9820-6

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