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The effects of PAR ablation on cartilage degradation and chondrocyte metalloproteinase expression\/activity were studied in cultures of mouse femoral head tissue with or without interleukin\u20101\u03b1 (IL\u20101\u03b1). At 1 week post\u2010DMM, synovial expression of cytokines and metalloproteinase genes was measured by reverse transcription\u2013polymerase chain reaction, and populations of inflammatory cells were quantified by flow cytometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Deletion of PAR\u20102, but not that of PAR\u20101, in mice significantly delayed the progression of cartilage damage and inhibited subchondral bone sclerosis following DMM. There was no inhibitory effect of PAR\u20101 or PAR\u20102 ablation on IL\u20101\u03b1\u2013induced cartilage degradation or chondrocyte metalloproteinase expression\/activation. A low but significant level of synovitis persisted in mice subjected to DMM compared to that in control mice subjected to sham surgery, but no differences between the genotypes were seen 4 or 8 weeks post\u2010DMM. One week after DMM, increased synovial expression of proinflammatory cytokines and metalloproteinase genes, along with increased levels of CD4+ T cells, inflammatory monocytes, and activated macrophages, were seen in all genotypes. However, there was a significant reduction in the percentage of activated macrophages in PAR\u20102<jats:sup>\u2212\/\u2212<\/jats:sup> mice compared to PAR\u20101<jats:sup>\u2212\/\u2212<\/jats:sup> and WT mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Deletion of PAR\u20102, but not that of PAR\u20101, results in a significant decrease in DMM\u2010induced cartilage damage. The chondroprotection in PAR\u20102<jats:sup>\u2212\/\u2212<\/jats:sup> mice appears to occur indirectly through modulation of extracartilaginous events such as subchondral bone remodeling and synovial macrophage activation, rather than through alteration of chondrocyte catabolic responses.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.38876","type":"journal-article","created":{"date-parts":[[2014,9,8]],"date-time":"2014-09-08T15:54:00Z","timestamp":1410191640000},"page":"3337-3348","source":"Crossref","is-referenced-by-count":115,"title":["Depletion of Protease\u2010Activated Receptor 2 but Not Protease\u2010Activated Receptor 1 May Confer Protection Against Osteoarthritis in Mice Through Extracartilaginous Mechanisms"],"prefix":"10.1002","volume":"66","author":[{"given":"Miriam T.","family":"Jackson","sequence":"first","affiliation":[{"name":"Kolling Institute of Medical Research and the University of Sydney at Royal North Shore Hospital, St. Leonards New South Wales 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