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Cartilage Destruction in Collagen Induced Arthritis Assessed with a New Biochemical Marker for Collagen Type II C-Telopeptide Fragments
TAKESHI ISHIKAWA, FUSAKO NISHIGAKI, STEPHAN CHRISTGAU, TAKAHISA NOTO, JOHN MO, NIELS FROM, KYOKO MINOURA, YOSHITAKA HIRAYAMA, YOSHITAKA OHKUBO, and SEITARO MUTOH
ABSTRACT.
Methods. Bovine articular cartilage explants were cultured in the presence of interleukin 1a, oncostatin M, and plasminogen to induce cartilage degradation. CTX-II, CTX-I (C-telopeptide fragment of collagen type I), glycosaminoglycan, and hydroxyproline contents in culture supernatants were measured. CIA was induced in 12-week-old female Lewis rats by immunization with bovine type II collagen. The incidence and severity of arthritis were monitored by measuring paw swelling, and urinary levels of CTX-II and CTX-I were determined. The knee joints of rats were histopathologically examined after sacrifice. Results. CTX-II but not CTX-I levels correlated well with collagen degradation in bovine articular cartilage in vitro quantified by hydroxyproline release. Urinary CTX-II levels as well as paw volume of CIA rats were significantly higher than normal rats on Days 21, 28, and 42 and were apparently correlated with cartilage destruction, assessed histopathologically. Urinary CTX-I level began to increase on Day 21, but only on Day 42 was it significantly different between CIA and normal rats. The elevation in CTX-I level appeared to occur later than that of CTX-II, in accord with the more delayed onset of bone erosion in the CIA model of rheumatoid arthritis. Conclusion. Urinary CTX-II may be a useful marker for evaluation of dynamics of cartilage destruction in CIA rats. (J Rheumatol 2004;31:1174-9) Key Indexing Terms:
BIOLOGICAL MARKERS
From Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan, and Nordic Bioscience Diagnostics A/S, Herlev, Denmark. T. Ishikawa, BS; F. Nishigaki, PhD; T. Noto, BS; K. Minoura, BS; Y. Hirayama, PhD; Y. Ohkubo, PhD; S. Mutoh, PhD, Fujisawa Pharmaceutical Co., Ltd.; S. Christgau, PhD; J. Mo, PhD; N. From, PhD, Nordic Bioscience Diagnostics A/S. Address reprint requests to Dr. F. Nishigaki, Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., 2-1-6, Kashima, Yodogawa-ku, Osaka 532-8514, Japan. E-mail: fusako_nishigaki@po.fujisawa.co.jp Submitted June 2, 2003; revision accepted December 19, 2003.
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