Proteomic analysis of bone tissues of patients with osteonecrosis of the femoral head.
Osteonecrosis of the femoral head (ONFH) is a devastating disease that can result in a femoral head collapse. By proteomics analysis, we identified 1,967 proteins with two or more unique peptides from ONFH and from control bones with a false discovery rate of 4.8%. Using spectral counting, we identified 141 overexpressed and 56 underexpressed proteins comparing ONFH bones to the controls. GSEA (gene set enrichment analysis) revealed that proteins overexpressed in ONFH are enriched for gene sets related to multiple myeloma and adult T-cell lymphoma (ATL), and to JAK2-dependent genes. We confirmed the underexpression of CHST2 (isoform 1 of carbohydrate sulfotransferase 2), a key protein involved in biosynthesis of chondroitin sulfate proteoglycans, and the underexpression of GPCR26 (G-protein coupled receptor 26), a protein that mediates intracellular calcium mobilization, in ONFH bones compared to controls. Taken together, our data suggest that biosynthesis of chondroitin sulfate proteoglycans and cation transport and mobilization may be a key process involved in the pathogenesis of ONFH. Our analysis sheds new light on the understanding of the pathogenesis of ONFH.
Zhang
Huarong
H
Zhejiang-California Nanosystems Institute (ZCNI), Zhejiang University , Hangzhou 310029, People's Republic of China.
Zhang
Lei
L
Wang
Jun
J
Ma
Yingying
Y
Zhang
Jing
J
Mo
Fan
F
Zhang
Weiyi
W
Yan
Shigui
S
Yang
Guojing
G
Lin
Biaoyang
B
D000328:Adult; D000368:Aged; D001842:Bone and Bones / Q000737:chemistry* / Q000378:metabolism; D002853:Chromatography, Liquid / Q000379:methods; D005260:Female; D005270:Femur Head / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D005271:Femur Head Necrosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000378:metabolism; D020543:Proteome / Q000032:analysis*; D040901:Proteomics / Q000379:methods; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015238:Sulfotransferases / Q000378:metabolism; D053719:Tandem Mass Spectrometry / Q000379:methods; D000097811:Carbohydrate Sulfotransferases
D020033:Protein Isoforms; D020543:Proteome; D043562:Receptors, G-Protein-Coupled; D015238:Sulfotransferases; D000097811:Carbohydrate Sulfotransferases