Comparative analysis of serum proteomes: discovery of proteins associated with osteonecrosis of the femoral head.
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.
Tan
Xiaoyun
X
Department of Orthopedics, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China. tanxiaoyun@126.com
Cai
Daozhang
D
Wu
Yaoliang
Y
Liu
Bin
B
Rong
Limin
L
Chen
Zhusheng
Z
Zhao
Qichun
Q
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
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