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Human chondrocytes and<jats:italic>h<\/jats:italic>PSCs isolated from cartilages and synovium of Osteoarthritis (OA) patients were cultured with 10% fetal bovine serum media or serum free media before treatment with IL-1\u03b2, TGF-\u03b21, or Connective tissue growth factor (CTGF). The expression of PAR-2 was detected using reverse transcriptase-polymerase chain reaction (RT-PCR) and western blotting. Collagen zymography was performed to assess the activity of Matrix metalloproteinases-13 (MMP-13). It was demonstrated that IL-1\u03b2 induces PAR-2 expression via p38 pathway in<jats:italic>h<\/jats:italic>PSCs. This induction can be repressed by TGF-\u03b2 and was observed to persist for at least 48 hrs, suggesting that TGF-\u03b2 inhibits PAR-2 expression through multiple pathways. First of all, TGF-\u03b2 was able to inhibit PAR-2 activity by inhibiting IL-1\u03b2-induced p38 signal transduction and secondly the inhibition was also indirectly due to MMP-13 inactivation. Finally, TGF-\u03b2 was able to induce CTGF, and in turn CTGF represses PAR-2 expression by inhibiting IL-1\u03b2-induced phospho-p38 level. TGF-\u03b2 could prevent OA from progression with the anabolic ability to induce CTGF production to maintain extracellular matrix (ECM) integrity and to down regulate PAR-2 expression, and the anti-catabolic ability to induce Tissue inhibitors of metalloproteinase-3 (TIMP-3) production to inhibit MMPs leading to avoid PAR-2 over-expression. Because IL-1\u03b2-induced PAR-2 expressed in<jats:italic>h<\/jats:italic>PSCs might play a significantly important role in early phase of OA, PAR-2 repression by exogenous TGF-\u03b2 or other agents might be an ideal therapeutic target to prevent OA from progression.<\/jats:p>","DOI":"10.1186\/1423-0127-16-97","type":"journal-article","created":{"date-parts":[[2009,10,27]],"date-time":"2009-10-27T10:26:11Z","timestamp":1256639171000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["TGF-\u03b2 inhibits IL-1\u03b2-activated PAR-2 expression through multiple pathways in human primary synovial cells"],"prefix":"10.1186","volume":"16","author":[{"given":"Shin-Han","family":"Tsai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Thau","family":"Sheu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Chih","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiu-Tan","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng-Shiung","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien-Ho","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2009,10,23]]},"reference":[{"key":"97_CR1","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1097\/00075197-200005000-00007","volume":"3","author":"PM van der Kraan","year":"2000","unstructured":"Kraan van der PM, Berg van den WB: Anabolic and destructive mediators in osteoarthritis. 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