机械应力相关基因在骨关节炎软骨下骨的表达

背景：机械应力改变是骨关节炎发生发展的关键因素。目的：观察机械应力相关基因在关节不稳所致的骨关节炎大鼠模型中软骨下骨的表达情况，为阐述机械应力因素在骨关节炎发病中的重要作用提供依据。方法：将SD大鼠分为实验组和对照组，每组30只。实验组行右膝内侧半月板及内侧副韧带切除术，对照组仅切开关节囊。分别于术后1，2，4周取右膝关节标本，提取软骨下骨的RNA，并采用全基因表达谱芯片技术研究软骨下骨全基因表达，根据现有文献报道，探索机械应力相关基因在该大鼠模型软骨下骨中的表达情况，并通过qRT—PCR对结果进行验证。结果与结论：发现3个重要的与机械应力相关的差异表达基因：Postn，Ihh，Bmp5，并由qRT—PCR得到验证：实验组中，Postn在术后第1周显著高表达，与对照组比较差异有显著性意义（P〈0．05），术后第2周也出现高表达的趋势，但与对照组比较差异无显著性意义（P〉0．05）。Bmp5也在术后第1周显著高表达，与对照组比较差异有显著性意义（P〈0．05），第2周及第4周也有高表达的趋势，但与对照组比较差异无显著性意义（P〉0．05）。lhh在术后第1周及第2周同时出现高表达，与对照组比较差异有显著性意义（P〈0．05）。结果可见机械应力因素是骨关节炎发病的重要因素，深入研究与其相关的基因或其通路，可能为揭示骨关节炎发病机制提供更多的依据，从而发现早期诊断及早期治疗的靶点。

Expression of mechanical stress related genes in subchondral bone of rat osteoarthritis model

BACKGROUND： Changes of mechanical stress is a key factor for the development of osteoarthritis. OBJECTIVE： To observe the expression of mechanical stress related genes in subchondral bone of rat osteoarthritis model caused by joint instability, and to provide basis for elaborating the effect of mechanical stress factors in the pathogenesis of osteoarthrltis. METHODS： Sprague Dawley rats were divided into two groups： experimental group and control group, 30 rats in each group. The right knee joints of experimental group underwent both medial collateral ligament resection and medial meniscectomy, while the control group just cut joint capsule. Rats were sacrificed at 1, 2 and 4 weeks after surgery to obtain the right knee joints. Total RNA of the subchondral bone was extracted, and the global gene expression of subchondral bone was researched with DNA microarray technology. The expression of mechanical stress related genes in subchondral bone of rat osteoarthritis model was explored according to the existing literatures, and then the results were identified through quantitative real-time PCR. RESULTS AND CONCLUSION： Three important mechanical stress related differentially expressed genes included： Postn, Ihh and Bmp5, and were confirmed by quantitative real-time PCR. In the experimental group, Postn was significantly expressed at 1 week after operation, and the difference between two groups was significant （P 〈 0.05）, and 2 weeks after operation, Postn was still highly expressed, but there was no significant difference between two groups （P 〉 0.05）. Bmp5 was significantly expressed at 1 week after operation, but the difference between two groups was significant （P 〈 0.05）, and at 2 weeks after operation, Bmp5 was highly expressed, but there was no significant difference between two groups （P 〉 0.05）. Ihh was highly expressed at 1 and 2 weeks after operation, and the difference between two groups was significant （P 〈 0.05）. Mechanical stress is the key stress in osteoarthritis. Further research of mechanical stress related genes and their pathway might provide more evidence for pathogenesis of osteoarthritis, thus discovering the targets for early diagnosis and early treatment.