Abstract
Osteonecrosis of the femoral head (ONFH) is the result of an interruption of the local circulation and the injury of vascular supply of bone. Multiple factors have been implicated in the development of the disease. However the mechanism of ischemia and necrosis in non-traumatic ONFH is not clear. The aim of our investigation was to identify genes that are differently expressed in ONFH vs. non-ONFH human bone and to describe the relationships between these genes using multivariate data analysis. Six bone tissue samples from ONFH male patients and 8 bone tissue samples from non-ONFH men were examined. The expression differences of selected 117 genes were analyzed by TaqMan probe-based quantitative real-time RT-PCR system. The significance test indicated marked differences in the expression of nine genes between ONFH and non-ONFH individuals. These altered genes code for collagen molecules, an extracellular matrix digesting metalloproteinase, a transcription factor, an adhesion molecule, and a growth factor. Canonical variates analysis demonstrated that ONFH and non-ONFH bone tissues can be distinguished by the multiple expression profile analysis of numerous genes controlled via canonical TGFB pathway as well as genes coding for extracellular matrix composing collagen type molecules. The markedly altered gene expression profile observed in the ONFH of human bone tissue may provide further insight into the pathogenetic process of osteonecrotic degeneration of bone.
Highlights
Primary femoral head osteonecrosis (ONFH) most commonly affects adults in the third and fourth decade of their life
Osteonecrosis of femoral head is the result of an interruption of the circulation, which leads to a disparity between the oxygen need of the bone cell and the ability of the local circulation to supply that need [1]
We have identified novel genes (SP7, COL1A2, COL5A2, COL10A1, ITGA2, MMP10, TNC, KL, vascular endothelial growth factor (VEGF)) that show marked alterations in their expression levels, and most of those have not yet been related to ONFH
Summary
Primary femoral head osteonecrosis (ONFH) most commonly affects adults in the third and fourth decade of their life. Osteonecrosis of femoral head is the result of an interruption of the circulation, which leads to a disparity between the oxygen need of the bone cell and the ability of the local circulation to supply that need [1]. The majority of the studies focused on gene polymorphisms affecting the coagulation system. Positive correlation was reported of factor V. gene Leiden mutation with primary ONFH. Plasminogen-activating inhibitor-1 (PAI-1) gene 4G/4G genotype and 5,10methylenetetrahydrofolate reductase (MTHFR) gene 677C/T heterozygote variant were over-presented in idiopathic ONFH patients. 4a/b variable number of tandem repeats (VNTR) polymorphism in intron 4 of nitric oxide synthase (eNOS) gene increased the risk of ONFH [3]. A comparative serum proteome analysis supports these genomic results and demonstrates that serum PAI-1 level is upregulated in
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