%0 Journal Article
%T Effects of Wnt3A and mechanical load on cartilage chondrocyte homeostasis
%A Rhian S Thomas
%A Alan R Clarke
%A Victor C Duance
%A Emma J Blain
%J Arthritis Research & Therapy
%D 2011
%I BioMed Central
%R 10.1186/ar3536
%X Chondrocytes were pre-stimulated with recombinant Wnt3A for 24 hours prior to the application of tensile strain (7.5%, 1 Hz) for 30 minutes. Activation of Wnt signalling, via ¦Â-catenin nuclear translocation and downstream effects including the transcriptional activation of c-jun, c-fos and Lef1, markers of chondrocyte phenotype (type II collagen (col2a1), aggrecan (acan), SOX9) and catabolic genes (MMP3, MMP13, ADAMTS-4, ADAMTS-5) were assessed.Physiological tensile strain induced col2a1, acan and SOX9 transcription. Load-induced acan and SOX9 expression were repressed in the presence of Wnt3A. Load induced partial ¦Â-catenin nuclear translocation; there was an additive effect of load and Wnt3A on ¦Â-catenin distribution, with both extensive localisation in the nucleus and cytoplasm. Immediate early response (c-jun) and catabolic genes (MMP3, ADAMTS-4) were up-regulated in Wnt3A stimulated chondrocytes. With load and Wnt3A there was an additive up-regulation of c-fos, MMP3 and ADAMTS-4 transcription, whereas there was a synergistic interplay on c-jun, Lef1 and ADAMTS-5 transcription.Our data suggest that load and Wnt, in combination, can repress transcription of chondrocyte matrix genes, whilst enhancing expression of catabolic mediators. Future studies will investigate the respective roles of abnormal loading and genetic predisposition in mediating cartilage degeneration.Articular cartilage functions in withstanding mechanical loads by dissipating applied loads across the joint surface; it also provides frictionless movement of joints. The biomechanical integrity of the tissue is dictated by the composition of the extracellular matrix (ECM); the ability of cartilage to undergo reversible deformation is attributed to its unique ECM architecture. Cartilage ECM comprises a highly hydrated network of collagen fibrils (types II, IX and XI) embedded in a gel of negatively charged proteoglycans which together provide the tissue with tensile strength to resist compressive lo
%U http://arthritis-research.com/content/13/6/R203