title: Inhibition of matrix metalloproteinase-13 expression in IL-1β-treated articular chondrocytes by a steroidal saponin, spicatoside A, and its cellular mechanisms of action.
abstract: Matrix metalloproteinase-13 (MMP-13) plays a critical role in degrading major collagens in human cartilage under some pathological conditions such as osteoarthritis. To establish the therapeutic potential against cartilage degradation, the effects of 12 naturally-occurring triterpenoids and steroids on MMP-13 induction were examined in the human chondrocyte cell line, SW1353. They included coreanoside F1, suavissimoside R1, spicatoside A, 25(S)-ruscogenin, methyl protogracillin, hederagenin, loniceroside A, loniceroside B, loniceroside C, smilaxin A, smilaxin C, and ursolic acid. Among these, only spicatoside A and 25(S)-ruscogenin were found to inhibit MMP-13 expression in IL-1β-treated SW1353 cells at a pharmacologically-relevant concentration of 10 μM. These effects were also supported by the finding that spicatoside A (20 μM) reduced glycosaminoglycan release from IL-1α-treated rabbit joint cartilage culture to some degree. When the cellular mechanisms of action of spicatoside A in MMP-13 inhibition were investigated, the blocking point was not found among the MMP-13 signaling molecules examined such as mitogen-activated protein kinases, activator protein-1, and nuclear transcription factor-κB. Instead, spicatoside A was found to reduce MMP-13 mRNA stability. All of these findings suggest that spicatoside A and 25(S)-ruscogenin have a therapeutic potential for protecting against cartilage breakdown in arthritic disorders.
authors.affiliation: College of Pharmacy, Kangwon National University, Chuncheon, 200-701, Korea.
authors.forename: Hyun
authors.initials: H
authors.lastname: Lim
authors.forename: Dong Suk
authors.initials: DS
authors.lastname: Min
authors.forename: Yuna
authors.initials: Y
authors.lastname: Kang
authors.forename: Hyeong Won
authors.initials: HW
authors.lastname: Kim
authors.forename: Kun Ho
authors.initials: KH
authors.lastname: Son
authors.forename: Hyun Pyo
authors.initials: HP
authors.lastname: Kim
mesh_terms: D000818:Animals; D002357:Cartilage Diseases / Q000188:drug therapy; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D002460:Cell Line; D019902:Chondrocytes / Q000187:drug effects / Q000201:enzymology*; D015536:Down-Regulation / Q000187:drug effects; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology*; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000096:biosynthesis* / Q000187:drug effects*; D016328:NF-kappa B / Q000378:metabolism; D010946:Plants, Medicinal / Q000737:chemistry; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D011817:Rabbits; D012503:Saponins / Q000494:pharmacology*; D013150:Spirostans / Q000494:pharmacology / Q000627:therapeutic use; D013256:Steroids / Q000494:pharmacology; D014315:Triterpenes / Q000494:pharmacology
chemical_list: C546003:5-(1-(glucopyranosyloxymethyl)ethenyl)-2-methyl-2-cyclohexen-1-one; D006025:Glycosaminoglycans; D053583:Interleukin-1beta; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D012503:Saponins; D013150:Spirostans; D013256:Steroids; D014315:Triterpenes; C012541:ruscogenin; D053509:Matrix Metalloproteinase 13