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作为自发性骨关节炎模型的STR/Ort小鼠尿生化标志物与骨密度的纵向分析

A longitudinal analysis of urinary biochemical markers and bone mineral density in STR/Ort mice as a model of spontaneous osteoarthritis.

作者信息

Sarukawa Junichiro, Takahashi Masaaki, Doi Mitsuhito, Suzuki Daisuke, Nagano Akira

机构信息

Hamamatsu University School of Medicine, Hamamatsu, Japan.

出版信息

Arthritis Rheum. 2010 Feb;62(2):463-71. doi: 10.1002/art.27202.

Abstract

OBJECTIVE

To investigate the longitudinal changes both in the urinary concentrations of biochemical markers and in bone mineral density (BMD) during disease progression in the STR/Ort mouse model of osteoarthritis (OA).

METHODS

Male STR/Ort mice were studied, with CBA mice used as nonarthritic controls. Radiographic evaluation and grading of the knee and measurements of urinary C-terminal crosslinking telopeptide of type II collagen (CTX-II), pyridinoline (Pyr), and deoxypyridinoline were performed between 8 weeks and 40 weeks of age. The BMD of the femoral shaft was measured from 20 weeks to 40 weeks of age and adjusted for body weight. Histologic evaluation and grading were performed at 40 weeks of age. STR/Ort mice were divided into 2 subgroups (STR OA and STR non-OA) based on histologic grading.

RESULTS

No significant differences between STR/Ort and CBA mice were observed for any biochemical marker or BMD at any time point. Urinary CTX-II levels and BMD in the STR OA subgroup were higher than those in the STR non-OA subgroup before radiographic changes of OA were apparent. Higher urinary Pyr levels in the STR OA subgroup were observed at the advanced stage of OA.

CONCLUSION

Urinary CTX-II could be a useful marker in the early diagnosis and predicting the progression of OA, and urinary Pyr may be a potential marker to assess the severity of OA at an advanced stage. An increase in BMD prior to the establishment of radiographic OA may be related to the induction of OA.

摘要

目的

在骨关节炎(OA)的STR/Ort小鼠模型疾病进展过程中,研究生化标志物尿浓度和骨密度(BMD)的纵向变化。

方法

对雄性STR/Ort小鼠进行研究,以CBA小鼠作为非关节炎对照。在8周龄至40周龄之间,对膝关节进行影像学评估和分级,并测量尿II型胶原C末端交联端肽(CTX-II)、吡啶啉(Pyr)和脱氧吡啶啉。在20周龄至40周龄之间测量股骨干的骨密度,并根据体重进行调整。在40周龄时进行组织学评估和分级。根据组织学分级将STR/Ort小鼠分为2个亚组(STR OA和STR非OA)。

结果

在任何时间点,STR/Ort小鼠和CBA小鼠之间在任何生化标志物或骨密度方面均未观察到显著差异。在OA的影像学改变明显之前,STR OA亚组的尿CTX-II水平和骨密度高于STR非OA亚组。在OA晚期观察到STR OA亚组的尿Pyr水平较高。

结论

尿CTX-II可能是OA早期诊断和预测疾病进展的有用标志物,尿Pyr可能是评估OA晚期严重程度的潜在标志物。在影像学OA确立之前骨密度增加可能与OA的诱导有关。

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