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转化生长因子-β1和结缔组织生长因子在大鼠膝关节固定模型关节囊中表达的研究

Expression of transforming growth factor-beta1 and connective tissue growth factor in the capsule in a rat immobilized knee model.

作者信息

Hagiwara Yoshihiro, Chimoto Eiichi, Takahashi Ichiro, Ando Akira, Sasano Yasuyuki, Itoi Eiji

机构信息

Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryomachi, Aobaku, Sendai, Japan 980-8574.

出版信息

Ups J Med Sci. 2008;113(2):221-34. doi: 10.3109/2000-1967-223.

Abstract

BACKGROUND

Contracture is a very common complication of joint immobilization in daily examination, but its cause is still unknown. A fibrotic change of the capsule is suggested to be one of the main causes of the joint contracture. The goal of this study was to analyze the expression pattern of transforming growth factor-beta1 (TGF-beta1) and connective tissue growth factor (CTGF), which are implicated in fibrosis in the capsule of a rat immobilized knee model.

MATERIALS AND METHODS

We immobilized the unilateral knee joints of 66 rats in 150 degrees of flexion using a plastic plate and metal screws. Sham operated knee joints of 66 rats had holes drilled and screws inserted but none of them were plated. The capsule from the anterior and posterior portion of the knee joints was harvested at 3 days, 1, 2, 4, 8 and 16 weeks after immobilization and the expression patterns of TGF-beta1 and CTGF were characterized using in situ hybridization and immunohistochemistry.

RESULTS

The in situ hybridization demonstrated that the mRNAs of both TGF-beta1 and CTGF increased continuously during the first 2 weeks after immobilization and then decreased. The response was relatively higher in the posterior capsule than in the anterior one. In contrast, the immunoreactivity of both TGF-beta1 and CTGF increased gradually with time. The response was much stronger in the posterior capsule than in the anterior one.

CONCLUSIONS

The capsule has a potency to produce TGF-beta1 and CTGF after immobilization. CTGF may play a role in causing and maintaining capsular fibrosis in collaboration with TGF-beta1. The fibrotic change in the posterior capsule may have resulted in limited motion in extension in this immobilized knee model in rats. It may be possible to prevent joint contractures by somehow blocking the fibrotic process.

摘要

背景

在日常检查中,挛缩是关节制动非常常见的并发症,但其病因仍不清楚。有人认为关节囊的纤维化改变是关节挛缩的主要原因之一。本研究的目的是分析转化生长因子-β1(TGF-β1)和结缔组织生长因子(CTGF)在大鼠膝关节制动模型关节囊中纤维化过程中的表达模式,这两种因子与纤维化有关。

材料与方法

我们用塑料板和金属螺钉将66只大鼠的单侧膝关节固定于150度屈曲位。66只假手术大鼠的膝关节钻孔并插入螺钉,但均未进行固定。在制动后3天、1、2、4、8和16周采集膝关节前后部的关节囊,采用原位杂交和免疫组织化学方法检测TGF-β1和CTGF的表达模式。

结果

原位杂交显示,制动后前2周内TGF-β1和CTGF的mRNA持续增加,随后下降。后关节囊的反应比前关节囊相对更高。相反,TGF-β1和CTGF的免疫反应性随时间逐渐增加。后关节囊的反应比前关节囊强得多。

结论

制动后关节囊有产生TGF-β1和CTGF的能力。CTGF可能与TGF-β1协同作用,在引起和维持关节囊纤维化中发挥作用。大鼠膝关节制动模型中后关节囊的纤维化改变可能导致伸展受限。通过某种方式阻断纤维化过程可能预防关节挛缩。

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