转化生长因子-β通路在早期创伤性骨性关节炎软骨下骨的动态变化

lne cnangmg expressions of transiormlng growm iacwr-neta signaling pamway In me suDcnonflrai bone in experimental early traumatic osteoarthritis

目的探讨转化生长因子-β（TGF—B）信号通路在早期创伤性骨性关节炎软骨下骨的动态改变情况，以揭示其在骨性关节炎致病中所起的作用。方法取30只雄性sD大鼠，随机分为实验组（n=15）和对照组（n=15）。实验组切除右膝内侧半月板及内侧副韧带，对照组仅切开关节囊。于术后1、2、4周取右膝关节标本，采用全基因表达谱芯片技术研究软骨下骨的全基因表达，利用信号通路分析、差异基因分析的方法分析TGF-β信号通路的动态改变情况。结果术后1、2周实验组与对照组TGF—β信号通路比较差异均有统计学意义（P〈0．05），术后4周两组比较差异无统计学意义（P〉0．05）。与TGF．B信号通路相关的差异表达基因包括：激活素A受体一1、激活素A受体．2b、抗苗勒管激素、骨形态发生蛋白-4、骨形态发生蛋白-5、骨形态发生蛋白受体-1a、软骨低聚物基质蛋白、核心蛋白多糖、干扰素儿抑制素β-a、头蛋白、SMAD特异性雌三醇泛素蛋白连接酶2、TGF-1β、TGF-132、TGF—βl受体、凝血酶敏感素一2、凝血酶敏感素-4前体、DNA结合抑制物4，FYVE区包含锌指类似物-16前体。结论TGF—β信号通路在早期创伤性骨性关节炎的软骨下骨改变中起重要作用，其作用具有时问特殊性。

Objective To study the expressions of transforming growth factor-beta（TGF-β） signaling pathway in the subchondral bone in experimental early traumatic osteoarthritis to understand the role of TGF-β signaling pathway in the pathogenesis of osteoarthlitis. Methods Thirty male SD rats were randomized into 2 equal groups. In the experimental group, the medial meniscus and the medial collateral ligament （MCL） of the right knee joint were exsected while the articular capsule was only cut open in the control group. Samples of the light knee joint were harvested at 1, 2 and 4 weeks postsurgery. Total RNA of the subchondral bone was extracted and then hybridized to Agilent Whole Rat Genome Microarray. Analyses of the pathway and differentially expressed genes were conducted to explore changes in the expression of the TGF-~3 signaling path- way. Results Significant differences in the expression of TGF-β signaling pathway between the experi- mental group and the control group were found at 1 and 2 weeks postsurgery （ P 〈 0. 05）, but not at 4 weeks postsurgery （P 〉 0. 05） . The following differentially expressed genes were found to be involved in the changing expressions of TGF-J3 signaling pathway： aetivin A receptor-I, activin A receptor-2b, anti-mullerian hormone, bone morphogenetic protein-d, bone morphogenetic protein-5, bone morphogenetic protein receptor-la, cartilage oligomelic matrix protein, decorin, interferon gamma, inhibin beta-A, noggin, SMAD specific E3 ubiquitin protein ligase-2, transforming growth factor-beta 1, transforming growth factor-beta 2, transforming growth fac- tor-beta receptor 1, thrombospondin-2, thrombospondin-4 precursor, inhibitor of DNA binding 4 and FYVE domain containing 16 （predicted） similar to Zinc finger. Conclusions TGF-β signaling pathway may play an important role in the pathogenesis of experimental early traumatic osteoarthritis in a time-dependent manner.