title: Effect of body-weight loading onto the articular cartilage on the occurrence of quinolone-induced chondrotoxicity in juvenile rats.
abstract: The effect of body-weight loading onto the articular cartilage on the occurrence of chondrotoxicity was investigated in male juvenile Sprague-Dawley rats given ofloxacin (OFLX) orally once at 900 mg/kg. Just after dosing of OFLX, hindlimb unloading was performed for 0, 2, 4, or 8 h by a tail-suspension method. Animals were sacrificed at 8h post-dose, and then the distal femoral articular cartilage was subjected to a histological examination and an investigation for gene expression of tumor necrosis factor receptor superfamily, member 12a (Tnfrsf12a); prostaglandin-endoperoxide synthase 2 (Ptgs2); plasminogen activator, urokinase receptor (Plaur); and matrix metalloproteinase 3 (Mmp3) by qRT-PCR analysis. As a result, cartilage lesions and up-regulations of these 4 genes that were seen in rats without the tail suspension were not observed in rats with the 8-h tail suspension, and a tendency to decrease in the incidence of the cartilage lesions and the gene expression was noted in a tail-suspension time dependent manner. Our results clearly indicate that body-weight loading onto the cartilage is necessary to induce cartilage lesions and gene expression of Tnfrsf12a, Ptgs2, Plaur, and Mmp3 in juvenile rats treated with OFLX.
authors.affiliation: Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd., 1-16-13 Kita-Kasai, Edogawa-ku, Tokyo 134-8630, Japan. goto.koichi.s7@daiichisankyo.co.jp
authors.forename: Koichi
authors.initials: K
authors.lastname: Goto
authors.forename: Masako
authors.initials: M
authors.lastname: Imaoka
authors.forename: Mayumi
authors.initials: M
authors.lastname: Goto
authors.forename: Isamu
authors.initials: I
authors.lastname: Kikuchi
authors.forename: Takami
authors.initials: T
authors.lastname: Suzuki
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Jindo
authors.forename: Wataru
authors.initials: W
authors.lastname: Takasaki
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D019417:Hindlimb Suspension / Q000379:methods; D006651:Histocytochemistry; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D015242:Ofloxacin / Q000633:toxicity*; D012313:RNA / Q000737:chemistry / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator / Q000235:genetics / Q000378:metabolism; D000074050:TWEAK Receptor
chemical_list: D000900:Anti-Bacterial Agents; D018124:Receptors, Tumor Necrosis Factor; D055293:Receptors, Urokinase Plasminogen Activator; D000074050:TWEAK Receptor; C000613300:Tnfrsf12a protein, rat; D012313:RNA; D015242:Ofloxacin; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D019278:Matrix Metalloproteinase 3