CAJ | 학술논문

目的利用基因芯片技术,研究骨关节炎关节软骨细胞基因表达谱差异性基因、差异性基因功能及通路,初步探讨骨关节炎预警基因.方法入选行关节置换术的骨关节炎、类风湿关节炎(RA)和无关节炎的创伤患者各3例,分成骨关节炎组、RA组和创伤组.分别取关节软骨标本,体外培养关节软骨细胞.采用人类全基因组寡核苷酸微阵列芯片技术,通过微阵列差异性基因分析软件两因素不配对检验分析比较骨关节炎组分别与创伤组、RA组关节软骨细胞基因表达谱的差异在生物分子功能注释系统中分析差异性基因功能、通路.结果骨关节炎组与创伤组比较差异基因为145个(其中70个上调,75个下调),骨关节炎组与RA组比较差异基因为281个(其中94个上调,187个下调)；骨关节炎组分别与创伤组、RA组比较得到的差异性表达基因功能分属于细胞过程、生理过程、细胞成分、生物调节、信号转导等；有统计学意义的差异性基因通路主要有:凋亡通路、细胞周期通路、P53蛋白信号通路、Fas 信号通路、一氧化氮通路、凋亡级联通路、局部黏附通路、细胞外基质受体相互作用通路、紧密连接通路、黏着接合通路、肌动蛋白细胞骨架调节通路、骨重塑通路、硫酸软骨素生物合成通路、Jak-STAT信号通路、Wnt信号通路、Toll样受体信号通路、细胞间黏附信号通路、T细胞受体信号通路等(P＜0.05)；骨关节炎.创伤组和骨关节炎-RA组之间差异性基因功能及通路存在差异,同时也存在交叉.结论从差异性基因表达种数、生物学功能、通路分析三方面获得骨关节炎生物学信息,使得从基因表达人手寻找骨关节炎的早期预警指标成为可能.
목적 이용기인심편기술,연구골관절염관절연골세포기인표체보차이성기인、차이성기인공능급통로,초보탐토골관절염예경기인.방법 입선행관절치환술적골관절염、류풍습관절염(RA)화무관절염적창상환자각3례,분성골관절염조、RA조화창상조.분별취관절연골표본,체외배양관절연골세포.채용인류전기인조과핵감산미진렬심편기술,통과미진렬차이성기인분석연건량인소불배대검험분석비교골관절염조분별여창상조、RA조관절연골세포기인표체보적차이재생물분자공능주석계통중분석차이성기인공능、통로.결과 골관절염조여창상조비교차이기인위145개(기중70개상조,75개하조),골관절염조여RA조비교차이기인위281개(기중94개상조,187개하조)；골관절염조분별여창상조、RA조비교득도적차이성표체기인공능분속우세포과정、생리과정、세포성분、생물조절、신호전도등；유통계학의의적차이성기인통로주요유:조망통로、세포주기통로、P53단백신호통로、Fas 신호통로、일양화담통로、조망급련통로、국부점부통로、세포외기질수체상호작용통로、긴밀련접통로、점착접합통로、기동단백세포골가조절통로、골중소통로、류산연골소생물합성통로、Jak-STAT신호통로、Wnt신호통로、Toll양수체신호통로、세포간점부신호통로、T세포수체신호통로등(P＜0.05)；골관절염.창상조화골관절염-RA조지간차이성기인공능급통로존재차이,동시야존재교차.결론 종차이성기인표체충수、생물학공능、통로분석삼방면획득골관절염생물학신식,사득종기인표체인수심조골관절염적조기예경지표성위가능.
Objective To investigate the gene expression profiling of articular chondrocyte and the function and pathway of the differentially expressed genes in patients with osteoarthritis (OA) by using gene microarray technique.Methods Three patients with OA,three patients with rheumatoid arthritis (RA) and three traumatic controls without arthritis were selected and were divided into OA versus RA and OA versus the traumatic control groups,and their articular cartilage cells were cultivated.The gene expression profiling was performed by human genome oligonucleotide microarray technique.The differences of gene expression of the articular chondrocyte in OA versus RA group and OA versus the traumatic control group were compared respectively by two class unpaired test using significant analysis of microarray software.The function and pathway of these differentially expressed genes were analyzed by using the database of Molecule Annotation System.Results The number of differentially expressed genes was 145 when OA compared with the traumatic control,in which 70 were up-regulated and 75 were down-regulated; and the number was 281 when OA were compared with RA,in which 94 were up-regnlated and 187 were down-regulated.The Gene Onto-logy (GO) functions of the differentially expressed genes of OA in each group were related to pathological and immune courses including cellular process,physiological process,cell division,biological regulation and cell signal transduction.The statistically significant pathways of these genes in each group included apoptosis pathway,cell cycle pathway,P53 signaling pathway,Fas signaling pathway,NO pathway,apeptotic cascade pathway,focal adhesion pathway, ECM-receptor interaction pathway, tight junction pathway, adhesive bonding pathway,actin cytoskeleton regulation pathway,bone remodeling pathway,chondroitin sulfate biosynthesis pathway,Jak-STAT signaling pathway,Wnt signaling pathway,Toll recepor signaling pathway,cell adhesion molecules pathway,T cell receptor signaling pathway,and s o on (P＜0.05).They displayed not only marked dif-ferences in GO function and gene pathway of differentially expressed genes between OA versus RA group and OA versus the traumatic control group,but also displayed the significant overlapping of the differentially expressed genes and pathways between the two groups.Conclusion The differentially expressed genes and pathways of articular chondrocytes involve apoptosis,extracellular matrix and cytokines in OA,which contri-bute to further study of early warning genes of OA.