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YKL-39,一种人类软骨相关蛋白,可诱导小鼠患关节炎。

YKL-39, a human cartilage-related protein, induces arthritis in mice.

作者信息

Sakata M, Masuko-Hongo K, Tsuruha J, Sekine T, Nakamura H, Takigawa M, Nishioka K, Kato T

机构信息

Rheumatology, Immunology, and Genetics Program, Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan.

出版信息

Clin Exp Rheumatol. 2002 May-Jun;20(3):343-50.

PMID:12102470
Abstract

OBJECTIVE

To determine whether YKL-39, a recently cloned secretory protein of articular chondrocytes, is arthritogenic in mice.

METHODS

Recombinant YKL-39 (rYKL-39) was expressed and purified from E. coli. To induce arthritis in mice, rYKL-39 (1, 10 or 50 g in Freund's incomplete adjuvant) was injected into the right footpad of mice from four different strains (BALB/c, DBA/1J, C57BL/6 and ICR). The mice received a second immunization with rYKL-39 by intradermal injection into the root of the tail 10 days after the first immunization. Severity of arthritis was assessed by scoring each paw on a scale from 0 to 4. Sixty days after thefirst immunization, the mice were sacrificed and the joints were examined by immunohistochemistry and radiography. The anti-YKL-39 and anti type II-collagen (CII) antibody titres were also assayed using ELISA.

RESULTS

Immunization with YKL-39 induced arthritis in all strains of mice tested, among which BALB/c was most susceptible. Histological examination showed synovial proliferation and irregularity of the cartilage surface in YKL-39-injected BALB/c mice. Moreover radiographic analysis revealed pathological changes in these mice. The YKL-39-immunised mice produced not only anti-YKL-39 antibody but also antibody against type II collagen, suggesting a spreading of autoimmunity after YKL-39.

CONCLUSIONS

YKL-39, a cartilage-related protein, is found to induce arthritis accompanied by pathologic changes in bone and cartilage. A better understanding of the immune response against cartilage-related components including YKL-39 may help to elucidate the pathological processes of arthritic disorders.

摘要

目的

确定YKL - 39(一种最近克隆的关节软骨细胞分泌蛋白)在小鼠中是否具有致关节炎作用。

方法

从大肠杆菌中表达并纯化重组YKL - 39(rYKL - 39)。为诱导小鼠发生关节炎,将rYKL - 39(1、10或50μg溶于弗氏不完全佐剂中)注射到来自四种不同品系(BALB/c、DBA/1J、C57BL/6和ICR)小鼠的右足垫。首次免疫10天后,通过皮内注射rYKL - 39至小鼠尾根部进行第二次免疫。通过按0至4分对每只爪子评分来评估关节炎的严重程度。首次免疫60天后,处死小鼠并通过免疫组织化学和放射照相术检查关节。还使用酶联免疫吸附测定法检测抗YKL - 39和抗II型胶原(CII)抗体滴度。

结果

用YKL - 39免疫可在所有测试的小鼠品系中诱导关节炎,其中BALB/c最易感。组织学检查显示,注射YKL - 39的BALB/c小鼠出现滑膜增生和软骨表面不规则。此外,放射学分析揭示了这些小鼠的病理变化。用YKL - 39免疫的小鼠不仅产生抗YKL - 39抗体,还产生抗II型胶原抗体,表明YKL - 39免疫后自身免疫反应扩散。

结论

发现软骨相关蛋白YKL - 39可诱导关节炎,并伴有骨和软骨的病理变化。更好地了解针对包括YKL - 39在内的软骨相关成分的免疫反应可能有助于阐明关节炎疾病的病理过程。

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