title: Collagen degradation induced by the combination of IL-1alpha and plasminogen in rabbit articular cartilage explant culture.
abstract: To investigate the effect of plasminogen on cartilage catabolism, we assessed collagen degradation in rabbit articular cartilage explants treated with or without plasminogen and interleukin-1alpha (IL-1alpha). The combination of IL-1 alpha and plasminogen induced rapid collagen degradation, amounting to more than 60% of the total collagen by day 7, while neither IL-1alpha nor plasminogen alone had any effect. To examine the mechanism of collagen degradation induced by IL-1alpha and plasminogen, the matrix metalloproteinases (MMPs) in the culture supernatants were examined by ELISA, Western blotting and gelatin zymography. We found that the treatment with IL-1alpha induced MMP-1, MMP-3, and MMP-9. In addition, plasminogen converted the pro form of MMPs into the active form. Both a tissue inhibitor of metalloproteinases-1 (TIMP-1) and a synthetic hydroxamate MMP inhibitor prevented this collagen release. These results suggest that plasminogen causes collagen degradation via activation of MMPs induced by IL-1alpha.
authors.affiliation: Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Ibaraki.
authors.forename: S
authors.initials: S
authors.lastname: Saito
authors.forename: M
authors.initials: M
authors.lastname: Katoh
authors.forename: M
authors.initials: M
authors.lastname: Masumoto
authors.forename: S
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Y
authors.initials: Y
authors.lastname: Masuho
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002356:Cartilage / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D003094:Collagen / Q000187:drug effects / Q000378:metabolism*; D017364:Collagenases / Q000187:drug effects / Q000378:metabolism; D046508:Culture Techniques; D004359:Drug Therapy, Combination; D004586:Electrophoresis / Q000379:methods; D004789:Enzyme Activation / Q000187:drug effects; D005780:Gelatin / Q000737:chemistry / Q000378:metabolism; D018093:Gelatinases / Q000187:drug effects / Q000378:metabolism; D006023:Glycoproteins / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D020781:Matrix Metalloproteinase 1; D019278:Matrix Metalloproteinase 3 / Q000187:drug effects / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D008969:Molecular Sequence Data; D010958:Plasminogen / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D011817:Rabbits; D019714:Tissue Inhibitor of Metalloproteinases
chemical_list: D006023:Glycoproteins; D007375:Interleukin-1; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D019714:Tissue Inhibitor of Metalloproteinases; D005780:Gelatin; D010958:Plasminogen; D003094:Collagen; D017364:Collagenases; D018093:Gelatinases; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1