Ameye L G, Deberg M, Oliveira M, Labasse A, Aeschlimann J M, Henrotin Y
Nestlé Research Center, Lausanne, Switzerland.
Arthritis Rheum. 2007 Oct;56(10):3336-46. doi: 10.1002/art.22875.
Compared with wild-type (WT) mice, biglycan/fibromodulin double-deficient mice develop severe knee osteoarthritis. We undertook this study to compare type II collagen catabolism in the 2 genotypes and to compare the usefulness of 3 biomarkers of collagen degradation (C2C [also known as Col2-3/4C(long mono)] as well as the peptide Coll2-1 and its nitrated form, Coll2-1NO2) for evaluating collagen catabolism in vivo.
In 15 WT mice and 15 biglycan/fibromodulin double-deficient mice, we determined serum levels of C2C at ages 66 and 141 days, and we determined serum levels of Coll2-1 and Coll2-1NO2 at ages 49, 81, 95, and 141 days. Expression of the biomarkers in knee sections was examined using immunohistochemistry.
The mean concentrations of C2C and Coll2-1 were higher in biglycan/fibromodulin double-deficient mice at all time points. For C2C and Coll2-1, the ratio of the serum concentration in biglycan/fibromodulin double-deficient mice to that in WT mice (the double-deficient:WT ratio) was constant over time and was approximately 1.63 and approximately 1.15, respectively. In contrast, the double-deficient:WT ratio for Coll2-1NO2 varied and, depending on age, was >1 or <1. No significant correlation was found between the expression of the different biomarkers, except for a weak, negative correlation between Coll2-1NO2 and C2C. In both genotypes, antibodies to each biomarker labeled some fibroblasts in the tendons and menisci as well as chondrocytes above the tidemark in articular cartilage. Growth plates were unstained. For each biomarker, extracellular staining was limited to fibrocartilage areas in the tendons and menisci in all mice and was limited to some focal lesions of the cartilage in biglycan/fibromodulin double-deficient mice.
The different double-deficient:WT ratios observed with C2C, Coll2-1, and Coll2-1NO2 in the absence of any correlation between the expression of the 3 biomarkers indicate that these biomarkers give complementary, rather than redundant, information about in vivo type II collagen catabolism.
与野生型（WT）小鼠相比，双糖链蛋白聚糖/纤调蛋白双缺陷小鼠会发展为严重的膝关节骨关节炎。我们开展本研究以比较两种基因型中II型胶原蛋白的分解代谢，并比较三种胶原蛋白降解生物标志物[C2C（也称为Col2 - 3/4C（长单峰））以及肽Coll2 - 1及其硝化形式Coll2 - 1NO2]在体内评估胶原蛋白分解代谢的效用。
在15只WT小鼠和15只双糖链蛋白聚糖/纤调蛋白双缺陷小鼠中，我们测定了66日龄和141日龄时的血清C2C水平，并测定了49日龄、81日龄、95日龄和141日龄时的血清Coll2 - 1和Coll2 - 1NO2水平。使用免疫组织化学检查膝关节切片中生物标志物的表达。
在所有时间点，双糖链蛋白聚糖/纤调蛋白双缺陷小鼠中C2C和Coll2 - 1的平均浓度均较高。对于C2C和Coll2 - 1，双糖链蛋白聚糖/纤调蛋白双缺陷小鼠与WT小鼠的血清浓度比（双缺陷：WT比）随时间保持恒定，分别约为1.63和约1.15。相比之下，Coll2 - 1NO2的双缺陷：WT比有所变化，且根据年龄不同，大于1或小于1。除了Coll2 - 1NO2与C2C之间存在微弱的负相关外，未发现不同生物标志物的表达之间存在显著相关性。在两种基因型中，针对每种生物标志物的抗体标记了肌腱和半月板中的一些成纤维细胞以及关节软骨中潮标上方的软骨细胞。生长板未被染色。对于每种生物标志物，细胞外染色在所有小鼠中仅限于肌腱和半月板的纤维软骨区域，在双糖链蛋白聚糖/纤调蛋白双缺陷小鼠中仅限于软骨的一些局灶性病变。
在三种生物标志物的表达之间不存在任何相关性的情况下，观察到C2C、Coll2 - 1和Coll2 - 1NO2不同的双缺陷：WT比，这表明这些生物标志物提供了关于体内II型胶原蛋白分解代谢的互补而非冗余信息。
