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采用一种针对II型胶原C-末端肽片段的新生化标志物评估胶原诱导性关节炎中的软骨破坏情况。

Cartilage destruction in collagen induced arthritis assessed with a new biochemical marker for collagen type II C-telopeptide fragments.

作者信息

Ishikawa Takeshi, Nishigaki Fusako, Christgau Stephan, Noto Takahisa, Mo John, From Niels, Minoura Kyoko, Hirayama Yoshitaka, Ohkubo Yoshitaka, Mutoh Seitaro

机构信息

Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.

出版信息

J Rheumatol. 2004 Jun;31(6):1174-9.

Abstract

OBJECTIVE

To assess the ability of a marker of collagen type II degradation (CTX-II) to quantify cartilage turnover in vitro in cartilage explants and in vivo in rats with collagen induced arthritis (CIA).

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.

摘要

目的

评估II型胶原降解标志物(CTX-II)在体外软骨外植体及胶原诱导性关节炎(CIA)大鼠体内定量软骨周转的能力。

方法

牛关节软骨外植体在白细胞介素1α、制瘤素M和纤溶酶原存在的情况下进行培养以诱导软骨降解。测量培养上清液中CTX-II、CTX-I(I型胶原C端肽片段)、糖胺聚糖和羟脯氨酸的含量。用牛II型胶原免疫12周龄雌性Lewis大鼠诱导CIA。通过测量爪肿胀监测关节炎的发病率和严重程度,并测定尿液中CTX-II和CTX-I的水平。处死大鼠后对膝关节进行组织病理学检查。结果:体外培养的牛关节软骨中,通过羟脯氨酸释放定量的胶原降解与CTX-II水平而非CTX-I水平密切相关。在第21、28和42天,CIA大鼠的尿CTX-II水平以及爪体积显著高于正常大鼠,并且与组织病理学评估的软骨破坏明显相关。尿CTX-I水平在第21天开始升高,但仅在第42天CIA大鼠与正常大鼠之间存在显著差异。CTX-I水平的升高似乎比CTX-II出现得晚,这与类风湿性关节炎CIA模型中骨侵蚀的发病延迟更为一致。

结论

尿CTX-II可能是评估CIA大鼠软骨破坏动态变化的有用标志物。

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