Song J, Wu J, Poulet B, Liang J, Bai C, Dang X, Wang K, Fan L, Liu R
Department of Orthopaedics, The Second Affiliated Hospital, Xi'an Jiaotong University, NO.157, Xiwu Road, Xi'an, Shaanxi, 710004, PR China.
Department of Orthopaedics, The Second Affiliated Hospital, Xi'an Jiaotong University, NO.157, Xiwu Road, Xi'an, Shaanxi, 710004, PR China; Department of Orthopaedics, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, Henan Province, 471009, PR China.
Osteoarthritis Cartilage. 2021 Jul;29(7):1081-1092. doi: 10.1016/j.joca.2021.04.005. Epub 2021 Apr 21.
The cartilage degeneration that accompanies subchondral bone necrosis plays an important role in the development of osteonecrosis of femoral head (ONFH). To better understand the molecular basis of cartilage degradation in ONFH, we compared the proteomic profiles of ONFH cartilage with that of fracture control.
Hip cartilage samples were collected from 16 ONFH patients and 16 matched controls with femoral neck fracture. Proteomics analysis was conducted using tandem mass tag-based quantitation technique. Gene ontology (GO) analysis, KEGG pathway and protein-protein interaction analysis were used to investigate the functions of the altered proteins and biological pathways. Differentially expressed proteins including alpha-2-HS-glycoprotein (AHSG) and Cytokine-like protein 1 (Cytl1) were validated by Western blot (WB) and immunohistochemistry (IHC).
303 differentially expressed proteins were identified in ONFH cartilage with 72 up-regulated and 231 down-regulated. Collagen turnover, glycosaminoglycan biosynthesis, metabolic pathways, and complement and coagulation cascades were significantly modified in ONFH cartilage. WB and IHC confirmed the increased expression of AHSG and decreased expression of Cytl1 in ONFH cartilage.
Our results reveal the implication of altered protein expression in the development of ONFH, and provide novel clues for pathogenesis studies of cartilage degradation in ONFH.
伴随软骨下骨坏死的软骨退变在股骨头坏死(ONFH)的发展中起重要作用。为了更好地理解ONFH中软骨降解的分子基础,我们比较了ONFH软骨与骨折对照的蛋白质组学图谱。
从16例ONFH患者和16例匹配的股骨颈骨折对照中收集髋部软骨样本。使用基于串联质量标签的定量技术进行蛋白质组学分析。基因本体(GO)分析、KEGG通路和蛋白质-蛋白质相互作用分析用于研究改变的蛋白质的功能和生物学途径。通过蛋白质免疫印迹(WB)和免疫组织化学(IHC)验证差异表达的蛋白质,包括α-2-HS-糖蛋白(AHSG)和细胞因子样蛋白1(Cytl1)。
在ONFH软骨中鉴定出303种差异表达的蛋白质,其中72种上调,231种下调。ONFH软骨中的胶原周转、糖胺聚糖生物合成、代谢途径以及补体和凝血级联反应均有显著改变。WB和IHC证实ONFH软骨中AHSG表达增加,Cytl1表达减少。
我们的结果揭示了蛋白质表达改变在ONFH发展中的意义,并为ONFH中软骨降解的发病机制研究提供了新线索。