背景:股骨头缺血性坏死(AVNFH)是一种进行性,多因素,引起髋关节疼痛和髋关节功能丧失的具有挑战性的临床疾病。到现在为止,AVNFH的发病机制尚不完全清楚。在这项研究中,我们使用蛋白质组学技术对AVNFH患者的软骨蛋白谱进行了表征,并鉴定了参与AVNFH进展的潜在蛋白.
方法:从6例患者(3例AVNFH患者和3例骨折患者)的软骨中提取并使用无标记蛋白质组学进行鉴定。将AVNFH反应蛋白与骨折患者的蛋白进行比较,并得到适当鉴定。生物信息学分析,包括基因本体论(GO),KEGG,和STRING进行鉴定AVNFH反应蛋白的功能。
结果:从患者的软骨组织中鉴定出总共1512种蛋白质。与骨折患者相比,在患有AVNFH的患者的软骨组织中鉴定出255个显著改变的蛋白质。功能分类表明,显著变化的蛋白质主要参与ECM-受体相互作用,病灶粘连,和糖酵解途径。有趣的是,脂肪细胞增强子结合蛋白1、细胞骨架相关蛋白4和ASPN蛋白显著下降,然而,抗白细胞蛋白酶,红细胞膜蛋白,溶菌酶c在AVNFH患者中高度升高。
结论:目前的蛋白质组学结果表明ECM-受体相互作用和粘着斑相关蛋白有助于AVNFH的发展。据我们所知,这是首次报道AVNFH患者软骨组织的蛋白质组学研究。包括小窝相关蛋白3和前胶原赖氨酸2-氧戊二酸5-双加氧酶2在内的标记蛋白可以帮助我们了解AVNFH的发病机理。
BACKGROUND: Avascular necrosis of the femoral head (AVNFH) is a progressive, multifactorial, and challenging clinical disease that causes hip pain and loss of hip joint function. Till now, the pathogenesis of AVNFH was not fully understood. In this study, we characterized cartilage protein profiles of patients with AVNFH and identified the potential proteins involved in the progress of AVNFH using proteomics technique.
METHODS: Proteins from the cartilage of 6 patients (3 AVNFH patients and 3 fracture patients) were extracted and identified using label-free proteomics. AVNFH-responsive proteins were compared with those of the fracture patients and duly identified. Bioinformatics analyses including gene ontology (GO), KEGG, and STRING were performed to identify the functions of AVNFH-responsive proteins.
RESULTS: A total of 1512 proteins were identified from cartilage tissues of the patients. Compared to fracture patients, 255 significantly changed proteins were identified in cartilage tissues of patients with AVNFH. Functional categorization indicated that the significantly changed proteins were mainly involved in ECM-receptor interaction, focal adhesion, and glycolysis pathways. Interestingly, adipocyte enhancer-binding protein 1, cytoskeleton-associated protein 4, and ASPN protein were dramatically decreased, however, anti leukoproteinase, erythrocyte membrane protein, and lysozyme c were highly increased in patients with AVNFH.
CONCLUSIONS: The current proteomic results suggest that ECM-receptor interaction and focal adhesion related proteins contribute to development of AVNFH. To our knowledge, this is firstly reported proteomic study on cartilage tissues of patients with AVNFH. The marker proteins including caveolae-associated protein 3 and procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 could help us to understand the pathogenesis of AVNFH.