title: Comparative analysis of serum proteomes: discovery of proteins associated with osteonecrosis of the femoral head.
abstract: No means exist to evaluate the activity status, turnover, and prognosis of idiopathic osteonecrosis of the femoral head (IONFH) except for X-ray evidence of segmental collapse as a very good marker for prognosis. Moreover, the only current method for diagnosis of this disease is through physical examination and diagnostic imaging results, and no serum biochemical markers exist. A comparative analysis of serum proteomes was performed to discover proteins associated with osteonecrosis of the femoral head. Two-dimensional electrophoresis (2-DE) patterns of human sera from 10 patients with IONFH and 10 normal subjects were analyzed. The differentially expressed spots were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), and 7 proteins were found. The expression levels of tissue-type plasminogen activator (t-PA), bone-carboxyglutamate protein (BGP), c-sis, and an unknown protein were downregulated in the sera of patients with IONFH, whereas the other 3 proteins, including plasminogen activator inhibitor type 1 (PAI-1), crosslaps, and anti-p53 antibody, were upregulated. To examine their applicability as diagnostic markers, levels of the 6 identified proteins in serum were validated from patients with IONFH, osteoarthritis (OA), rheumatoid arthritis (RA), and fracture using the enzyme-linked immunosorbent assay (ELISA) method. It was found that only serum levels of t-PA, PAI-1, crosslaps, and anti-p53 antibody in patients with IONFH were always significantly different from those in patients with OA, RA, and fracture. These results suggest that serum levels of t-PA, PAI-1, crosslaps, and anti-p53 antibody could be used as noninvasive diagnostic biomarkers for IONFH.
authors.affiliation: Department of Orthopedics, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China. tanxiaoyun@126.com
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Tan
authors.forename: Daozhang
authors.initials: D
authors.lastname: Cai
authors.forename: Yaoliang
authors.initials: Y
authors.lastname: Wu
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.forename: Limin
authors.initials: L
authors.lastname: Rong
authors.forename: Zhusheng
authors.initials: Z
authors.lastname: Chen
authors.forename: Qichun
authors.initials: Q
authors.lastname: Zhao
mesh_terms: D015055:1-Carboxyglutamic Acid / Q000097:blood; D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000737:chemistry* / Q000302:isolation & purification; D003094:Collagen / Q000097:blood; D015180:Electrophoresis, Gel, Two-Dimensional; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005271:Femur Head Necrosis / Q000097:blood* / Q000175:diagnosis / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D040901:Proteomics / Q000379:methods*; D020574:Proto-Oncogene Proteins c-sis / Q000097:blood; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D010959:Tissue Plasminogen Activator / Q000097:blood; D016159:Tumor Suppressor Protein p53 / Q000276:immunology
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D010446:Peptide Fragments; D017395:Plasminogen Activator Inhibitor 1; D020574:Proto-Oncogene Proteins c-sis; C051321:SERPINE1 protein, human; D016159:Tumor Suppressor Protein p53; C110762:glutamyl-lysyl-alanyl-histidyl-aspartyl-glycyl-glycyl-arginine; D015055:1-Carboxyglutamic Acid; D003094:Collagen; D010959:Tissue Plasminogen Activator