Conclusion
Overall, our data reveal blockade of IL-33 signalling as a viable therapeutic target for OA.
Methods
Non-OA and OA human chondrocytes samples were examined for IL-33 and ST2 expression. Novel inducible cartilage specific knockout mice (IL-33Acan CreERT2) and inducible fibroblast-like synoviocyte knockout mice (IL-33Col1a2 CreERT2) were generated and subjected to an experimental OA model. In addition, wild-type mice were intra-articularly administered with either IL-33- or ST2-neutralising antibodies during experimental OA studies.
Results
IL-33 and its receptor ST2 have increased expression in OA patients and a murine disease model. Administering recombinant IL-33 increased OA and pain in vivo. Synovial fibroblast-specific deletion of IL-33 decreased synovitis but did not impact disease outcomes, whilst cartilage-specific deletion of IL-33 improved disease outcomes in vivo. Blocking IL-33 signalling also reduced the release of cartilage-degrading enzymes in human and mouse chondrocytes. Most importantly, we show the use of monoclonal antibodies against IL-33 and ST2 attenuates both OA and pain in vivo.