title: Passive role of articular chondrocytes in quinolone-induced arthropathy in guinea pigs.
abstract: The role of articular chondrocytes and matrix degrading enzymes such as collagenase and neutral protease in the pathogenesis of quinolone-induced cartilage degeneration was investigated in immature guinea pigs. Articular cartilage from nalidixic acid (NA) treated guinea pigs was examined for the presence of protease activity or the ex vivo synthesis of collagenase at various times post-treatment. Histologic evaluation of knee joints confirmed the presence of degenerative changes in the matrix, but increased collagenase synthesis or protease activity were not detected. A separate group of animals was used to determine the importance of articular chondrocytes in the lesion generation. These cells were killed by intra-articular injection of the glycolysis inhibitor iodoacetic acid (IA) prior to treatment of the animals with NA. Typical "blister-like" their presence was not required for lesion development. Cartilage exposed to IA only did not exhibit "blister-like" lesions indicating that chondrocyte death and proteoglycan loss in conjunction with frictional forces associated with load-bearing were not sufficient to induce major matrical disruptive changes during the period of this study. These results indicate that articular chondrocytes are not actively involved in inducing the degenerative changes and provide no evidence for involvement of collagenase or neutral protease in the pathogenesis of the lesion.
authors.affiliation: Connective Tissue and Monoclonal Antibody Research, Eli Lilly and Co., Indianapolis, Indiana 46285.
authors.forename: A M
authors.initials: AM
authors.lastname: Bendele
authors.forename: J F
authors.initials: JF
authors.lastname: Hulman
authors.forename: A K
authors.initials: AK
authors.lastname: Harvey
authors.forename: P S
authors.initials: PS
authors.lastname: Hrubey
authors.forename: S
authors.initials: S
authors.lastname: Chandrasekhar
mesh_terms: D000818:Animals; D002357:Cartilage Diseases / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D002358:Cartilage, Articular / Q000187:drug effects / Q000201:enzymology / Q000473:pathology* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D006168:Guinea Pigs; D007461:Iodoacetates / Q000494:pharmacology; D008297:Male; D008666:Metalloendopeptidases / Q000378:metabolism; D003012:Microbial Collagenase / Q000378:metabolism; D009268:Nalidixic Acid / Q000494:pharmacology; D010447:Peptide Hydrolases / Q000378:metabolism; D015363:Quinolones / Q000633:toxicity*
chemical_list: D007461:Iodoacetates; D015363:Quinolones; D009268:Nalidixic Acid; D010447:Peptide Hydrolases; D008666:Metalloendopeptidases; D003012:Microbial Collagenase