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在胶原诱导性关节炎大鼠中,基质金属蛋白酶依赖性的软骨、滑膜和结缔组织的降解增加。

Matrix metalloproteinase-dependent turnover of cartilage, synovial membrane, and connective tissue is elevated in rats with collagen induced arthritis.

机构信息

Nordic Bioscience, Herlev, Denmark.

出版信息

J Transl Med. 2012 Sep 20;10:195. doi: 10.1186/1479-5876-10-195.

DOI:10.1186/1479-5876-10-195
PMID:22992383
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3551788/
Abstract

BACKGROUND

Rheumatoid arthritis is a disease affecting the extracellular matrix of especially synovial joints. The thickness of the synovial membrane increases and surrounding tissue degrades, leading to altered collagen balance in the tissues. In this study, we investigated the altered tissue balance of cartilage, synovial membrane, and connective tissue in collagen induced arthritis (CIA) in rats.

METHODS

Six newly developed ELISAs quantifying MMP-derived collagen degradation (C1M, C2M, and C3M) and formation (P1NP, P2NP, and P3NP) was used to detect cartilage turnover in rats with CIA. Moreover, CTX-II was used to detect alternative type II collagen degradation and as control of the model. 10 Lewis rats were injected with porcrine type II collagen twice with a 7 day interval and 10 rats was injected with 0.05 M acetic acid as control. The experiment ran for 26 days.

RESULTS

A significant increase in the degradation of type I, II, and III collagen (C1M, C2M, and C3M, respectively) was detected on day 22 (P = 0.0068, P = 0.0068, P < 0.0001, respectively), whereas no significant difference in formation (P1NP, P2NP, and P3NP) was detected at any time point (P=0.22, P=0.53, P=0.53, respectively). The CTX-II level increased strongly from disease onset and onwards.

CONCLUSION

A nearly total separation between diseased and control animals was detected with C3M, making it a good diagnostic marker. The balance of type I, II, and III collagen was significantly altered with CIA in rats, with favour of degradation of the investigated collagens. This indicates unbalanced turnover of the surrounding tissues of the synovial joints, leading to increased pain and degeneration of the synovial joints.

摘要

背景

类风湿关节炎是一种影响滑膜关节细胞外基质的疾病。滑膜膜的厚度增加,周围组织降解,导致组织中胶原蛋白平衡改变。在这项研究中,我们研究了胶原诱导性关节炎(CIA)大鼠中滑膜、滑膜膜和结缔组织中软骨胶原蛋白平衡的改变。

方法

使用 6 种新开发的 ELISA 定量检测 MMP 衍生的胶原蛋白降解(C1M、C2M 和 C3M)和形成(P1NP、P2NP 和 P3NP),以检测 CIA 大鼠软骨的周转率。此外,CTX-II 用于检测 II 型胶原蛋白的替代降解,并作为模型的对照。10 只刘易斯大鼠用猪 II 型胶原蛋白两次注射,间隔 7 天,10 只大鼠用 0.05 M 乙酸注射作为对照。实验持续 26 天。

结果

在第 22 天(P=0.0068,P=0.0068,P<0.0001,分别)检测到 I、II 和 III 型胶原蛋白(C1M、C2M 和 C3M,分别)的降解显著增加,而在任何时间点都未检测到形成(P1NP、P2NP 和 P3NP)的差异(P=0.22,P=0.53,P=0.53,分别)。CTX-II 水平从发病开始就急剧升高。

结论

用 C3M 检测到患病动物和对照动物之间几乎完全分离,使其成为一种良好的诊断标志物。CIA 大鼠的 I、II 和 III 型胶原蛋白平衡明显改变,降解 favour 所研究的胶原蛋白。这表明滑膜关节周围组织的周转率失衡,导致疼痛增加和滑膜关节退化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31c0/3551788/e10382293faf/1479-5876-10-195-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31c0/3551788/e2126a8768fc/1479-5876-10-195-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31c0/3551788/fc117f89873c/1479-5876-10-195-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31c0/3551788/aa2dc94cb6e2/1479-5876-10-195-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31c0/3551788/e10382293faf/1479-5876-10-195-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31c0/3551788/e2126a8768fc/1479-5876-10-195-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31c0/3551788/fc117f89873c/1479-5876-10-195-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31c0/3551788/aa2dc94cb6e2/1479-5876-10-195-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31c0/3551788/e10382293faf/1479-5876-10-195-4.jpg

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