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