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TNF-α and IL-6 differentially regulate Dkk-1 in the inflamed arthritic joint

Yeremenko N, Zwerina K, Rigter G, Pots D, Fonseca J, Zwerina J, Schett G, Baeten D. - Arthritis Rheumatol. 2015 May 4. doi: 10.1002/art.39183. [Epub ahead of print]

Different inflammatory joint diseases have distinct patterns of bone damage, but the molecular pathways determining each one remains poorly defined. This study investigates the wingless (Wnt)-signalling pathway, by analysing the expression of Dkk-1 (an inhibitor of the Wnt pathway) and its regulation by the pro-inflammatory cytokines TNF-α and IL-6 in SpA versus RA inflamed peripheral joints.

Findings from the study show an inverse correlation of Dkk-1 with IL-6 in vivo and a differential regulation of Dkk-1 production by TNF-α and IL-6 in vitro. Although limited by analysis only in peripheral joint inflammation, and only to two pro-inflammatory cytokines, results from this study may help to determine functional Wnt signalling and tissue remodelling in the arthritic joint.

Keywords: IL-6, Preclinical, MOA

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Upload date: June 2015

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