title: CIINE Reflects Collagenase-Specific CII Breakdown in Cartilage Explant and Whole Body of Canine.
abstract: To evaluate collagenase inhibitors for the treatment of osteoarthritis and to correlate them with clinical pathology, canine cartilage explant and anterior cruciate ligament transection (ACLT) models were examined by quantifying the CII neoepitope (CIINE). This peptide is a putative marker for collagenase-specific type II collagen (CII) degradation, which is a critical step in osteoarthritis pathology. The concentration of CIINE in supernatants of canine cartilage explants showed increase upon IL-1β-stimulation and collagenase inhibitors suppressed this elevation of CIINE. In the canine ACLT model, levels of CIINE in urine (uCIINE) increased as lesions of knee joint cartilage developed and decreased in response to collagenase inhibitors. Our results suggest that CIINE reflects collagenase-specific CII degradation in canine explants and whole bodies. It is anticipated that these data will establish a tool for clarifying and bridging the efficacy and mechanism of collagenase inhibitors at the preclinical stage of drug discovery.
authors.affiliation: Shionogi & Co., Ltd., Fukushima-ku, Osaka, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Matsukawa
authors.forename: Miki
authors.initials: M
authors.lastname: Tanimura
authors.forename: Tomoko
authors.initials: T
authors.lastname: Toyosaki-Maeda
authors.forename: Akihiro
authors.initials: A
authors.lastname: Noda
authors.forename: Mika
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Akira
authors.initials: A
authors.lastname: Yamauchi
authors.forename: Junji
authors.initials: J
authors.lastname: Onoda
authors.forename: Toshinaga
authors.initials: T
authors.lastname: Tsuji
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Takahashi
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Matsuo
authors.forename: Naoshi
authors.initials: N
authors.lastname: Fukui
keywords: CII neoepitope; biomarker; collagenase; matrix metalloproteinase; osteoarthritis; type II collagen