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CTX-II 水平在骨关节炎动物模型中的意义:一项为期 5 个月的纵向研究。

Significance of the serum CTX-II level in an osteoarthritis animal model: a 5-month longitudinal study.

机构信息

Université de Lyon, ISPB-Faculté de Pharmacie, École Nationale Vétérinaire de Lyon, UPSP 2007-03-135 RTI2B, France.

出版信息

Osteoarthritis Cartilage. 2010 Nov;18(11):1467-76. doi: 10.1016/j.joca.2010.07.007.

Abstract

OBJECTIVE

The aim of this study was to investigate the clinical value of serum measurement of C-telopeptide of type II collagen (CTX-II). In correlation with late stages of osteoarthritis (OA) evaluated with histological assessment, the evolution of serum CTX-II concentration was followed during a 20-week longitudinal study in rabbit anterior cruciate ligament transection (ACLT) OA model in adult and growing animals.

METHODS

OA was induced in five adult and nine growing rabbits. Four adult and four young rabbits were unoperated. Serum sampling was made at week 0, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16 and 20 after the surgery in all rabbits. Animals were euthanized 20 weeks after the surgery. Serum CTX-II levels were analyzed with a recently available enzyme-linked immunosorbent assay (ELISA) kit, the protocol of which has been modified to increase the sensitivity of the test.

RESULTS

Significant differences for the CTX-II levels at W3, W6, W8, W10, W12, W14, W16 and W20 were observed between the adult ACLT and the control groups. A negative correlation between CTX-II levels and cartilage thickness of the medial compartment of the knee at W8, W10, W12 and a positive correlation between the CTX-II levels and the histomorphological score of the medial compartment of the knee at W3, W6, W8, W10, W12 were noted in adult animals. In young animals, operated or not, we observed high CTX-II levels at the beginning of the study, which decreased until the end.

CONCLUSION

Our results suggest the interest of the serum CTX-II monitoring for the OA progression and the relevance of the multiple time point analysis of this biomarker. Moreover, they address the question of the importance of correctly choosing the age of the animals used in the pre-clinical studies of OA.

摘要

目的

本研究旨在探讨Ⅱ型胶原 C 端肽(CTX-II)血清测定的临床价值。通过与组织学评估评估的骨关节炎(OA)晚期相关,在兔前交叉韧带切断(ACLT)OA 模型的 20 周纵向研究中,我们对成年和生长中动物的血清 CTX-II 浓度的演变进行了跟踪。

方法

OA 在 5 只成年和 9 只生长兔中诱导。4 只成年和 4 只幼年兔子未进行手术。所有兔子均在手术后第 0、1、2、3、4、6、8、10、12、14、16 和 20 周进行血清取样。手术后 20 周处死动物。使用最近可用的酶联免疫吸附测定(ELISA)试剂盒分析血清 CTX-II 水平,该试剂盒的方案已进行了修改以提高测试的灵敏度。

结果

在 W3、W6、W8、W10、W12、W14、W16 和 W20 时,成年 ACLT 组和对照组的 CTX-II 水平存在显著差异。在成年动物中,CTX-II 水平与膝关节内侧间室软骨厚度呈负相关,在 W8、W10、W12 时;CTX-II 水平与膝关节内侧间室的组织形态学评分呈正相关,在 W3、W6、W8、W10、W12 时。在接受或未接受手术的幼年动物中,我们在研究开始时观察到高 CTX-II 水平,然后其水平逐渐降低。

结论

我们的结果表明,监测血清 CTX-II 对 OA 进展具有重要意义,并且该生物标志物的多次时间点分析具有相关性。此外,它们提出了在 OA 临床前研究中正确选择动物年龄的重要性问题。

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