Roles for the interleukin-4 receptor and associated JAK/STAT proteins in human articular chondrocyte mechanotransduction

S. J. Millward-Sadler, N. S. Khan, M. G. Bracher, M. O. Wright, D. M. Salter

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Objective: To identify functional interleukin-4 (IL4) receptor (IL4R) subtypes and associated Janus kinase/signal transducers and activators of transcription (JAK/STAT) molecules in human articular chondrocytes and assess the role of JAK/STAT proteins in chondrocyte mechanotransduction. Methods: Expression of IL4R subunits and associated molecules was assessed by immunohistochemistry and western blotting. Functional IL4R were identified by chemical crosslinking of IL4-stimulated chondrocytes and western blotting. JAK and STAT phosphorylation was assessed by western blotting. Results: Chondrocytes from normal and osteoarthritic (OA) cartilage express IL4Rα, γc and IL13Rα1 subunits (components of the Type I and Type II IL4R). In the presence of IL4 only functional Type II IL4Rs were identified in normal or OA chondrocytes. With the exception of STAT2, no differences in JAK/STAT expression were detected between normal and OA cartilage. STAT2 was expressed in OA but not normal chondrocytes. Mechanical stimulation (MS) resulted in an IL4R-dependent increase in phosphorylated Tyk2 in normal chondrocytes, which could be abolished by IL1β preincubation. No phosphorylation of STAT5 or STAT6 was detected in either normal or OA chondrocytes following mechanical stimulation (MS) IL4 stimulation resulted in a decrease in Tyk2 phosphorylation and an increase in phosphorylation of STAT6 in both normal and OA chondrocytes. Conclusion: Chondrocytes from normal and OA cartilage signal through a Type II IL4R. This signalling is via a STAT6-independent pathway. Differences in IL4 signalling are likely due to crosstalk between integrin and cytokine signalling pathways, and not differences in IL4R expression. © 2006 OsteoArthritis Research Society International.
    Original languageEnglish
    Pages (from-to)991-1001
    Number of pages10
    JournalOsteoarthritis and Cartilage
    Volume14
    Issue number10
    DOIs
    Publication statusPublished - Oct 2006

    Keywords

    • Chondrocyte
    • Cytokine
    • IL4 receptor
    • JAK/STAT
    • Mechanotransduction
    • Osteoarthritis

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