title: SKI306X suppresses cartilage destruction and inhibits the production of matrix metalloproteinase in rabbit joint cartilage explant culture.
abstract: SKI306X was previously found to have cartilage protective effects in the experimental osteoarthritis (OA) model. To investigate the chondro-protective benefits of SKI306X for its capacity in altering changes in cartilage metabolism and molecular mechanisms of cartilage protective action, SKI306X is studied in rabbit cartilage explants culture. To investigate the protective effect of SKI306X on cartilage catabolism, we assessed collagen degradation in rabbit cartilage explants treated with interleukin-1alpha up to 3 weeks. To examine the reaction mechanism, matrix metalloproteinase (MMPs) were investigated by fluorimetric and Western blotting analysis. In addition, its effects on the activation process of proenzyme MMP-3 were determined by gelatin zymography. SKI306X significantly inhibited collagen degradation and inhibited the activities of several MMPs. Total MMPs activities in cultured medium were substantially increased in the third week at the time of collagen degradation with the absence of SKI306. However, the introduction of SKI306X decreased MMPs activities in cultured medium. Furthermore, Western blotting analysis proved that these inhibitory effects of this drug were the result of inhibiting MMPs expression. SKI306X also inhibited the activation of proenzyme MMP-3 to the active form of MMP-3. These results indicate that SKI306X inhibits matrix degradation by down regulating MMPs expression and secretion, inhibition of MMPs activity, and inhibiting activation of MMP-3 during the collagen breakdown process.
authors: Life Science Research Center, SK Chemicals, Kyugki-Do, South Korea.
authors: Joo-Hyon
authors: JH
authors: Kim
authors: Keun-Ho
authors: KH
authors: Ryu
authors: Ki-Won
authors: KW
authors: Jung
authors: Chang-Kyun
authors: CK
authors: Han
authors: Wie-Jong
authors: WJ
authors: Kwak
authors: Yong-Baik
authors: YB
authors: Cho
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D017364:Collagenases / Q000096:biosynthesis; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D011817:Rabbits
chemical_list: D004365:Drugs, Chinese Herbal; D061965:Matrix Metalloproteinase Inhibitors; C460104:SKI 306X; D003094:Collagen; D017364:Collagenases; D053509:Matrix Metalloproteinase 13; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3