Landmann - Small molecule inhibitors of WNT-beta-catenin signaling block IL1beta-TNFalpha induced cartilage degradation

Ellie B.M. Landman, Razvan L. Miclea, Clemens A. van Blitterswijk,
Marcel Karperien

Arthritis Research & Therapy 2013


Introduction In this study, we tested the ability of small molecule inhibitors of WNT/β-
catenin signaling to block IL1β/TNFα induced cartilage degradation. Pro-inflammatory
cytokines like IL1β and TNFα are potent inducers of cartilage degradation by up-regulating
MMP expression and activity. Since WNT/β-catenin signaling was found to be involved in
IL1β/TNFα induced upregulation of MMP activity, we hypothesized that inhibition of
WNT/β-catenin signaling might block IL1β/TNFα induced cartilage degradation. We tested
the effect of small molecules that block the interaction between β-catenin and TCF/LEF
transcription factors on IL1β/TNFα induced cartilage degradation in mouse fetal metatarsals.