Mayo Clinic, 200First Street, Rochester, Minnesota, 55905, USA.
Bone Joint Res. 2014 Mar 26;3(3):82-8. doi: 10.1302/2046-3758.33.2000276. Print 2014.
The goal of this study was to determine whether intra-articular administration of the potentially anti-fibrotic agent decorin influences the expression of genes involved in the fibrotic cascade, and ultimately leads to less contracture, in an animal model.
A total of 18 rabbits underwent an operation on their right knees to form contractures. Six limbs in group 1 received four intra-articular injections of decorin; six limbs in group 2 received four intra-articular injections of bovine serum albumin (BSA) over eight days; six limbs in group 3 received no injections. The contracted limbs of rabbits in group 1 were biomechanically and genetically compared with the contracted limbs of rabbits in groups 2 and 3, with the use of a calibrated joint measuring device and custom microarray, respectively.
There was no statistical difference in the flexion contracture angles between those limbs that received intra-articular decorin versus those that received intra-articular BSA (66° vs 69°; p = 0.41). Likewise, there was no statistical difference between those limbs that received intra-articular decorin versus those who had no injection (66° vs 72°; p = 0.27). When compared with BSA, decorin led to a statistically significant increase in the mRNA expression of 12 genes (p < 0.01). In addition, there was a statistical change in the mRNA expression of three genes, when compared with those without injection.
In this model, when administered intra-articularly at eight weeks, 2 mg of decorin had no significant effect on joint contractures. However, our genetic analysis revealed a significant alteration in several fibrotic genes. Cite this article: Bone Joint Res 2014;3:82-8.
本研究旨在确定关节内给予潜在抗纤维化剂decorin 是否会影响纤维性级联反应中相关基因的表达,并最终导致动物模型中的挛缩程度减轻。
共 18 只兔子接受右膝关节手术形成挛缩。第 1 组的 6 个肢体接受了 4 次关节内 decorin 注射;第 2 组的 6 个肢体在 8 天内接受了 4 次关节内牛血清白蛋白(BSA)注射;第 3 组的 6 个肢体未接受注射。使用校准关节测量装置和定制微阵列分别对第 1 组挛缩肢体与第 2 组和第 3 组的挛缩肢体进行生物力学和基因比较。
关节内给予 decorin 与给予关节内 BSA 的肢体的屈曲挛缩角度无统计学差异(66°比 69°;p=0.41)。同样,关节内给予 decorin 与未注射的肢体之间也无统计学差异(66°比 72°;p=0.27)。与 BSA 相比,decorin 导致 12 个基因的 mRNA 表达显著增加(p<0.01)。此外,与未注射的相比,三个基因的 mRNA 表达也发生了统计学变化。
在该模型中,在 8 周时关节内给予 2mg decorin 对关节挛缩无明显影响。然而,我们的基因分析显示,几个纤维化基因发生了显著改变。
Bone Joint Res. 2014;3:82-8.