Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of human samples to identify markers for early diagnosis of of endoprosthesis loosening

ABSTRACT: The aim of the study was to identify markers for the early diagnosis of endoprosthesis loosening, for the differentiation between wear-particle induced and septic loosening, as well as to gather new insights into the pathogenesis. 824 genes were differentially expressed with a fold change greater than 2. Among these were Chitinase 1, CD52, Calpain 3, Apolipoprotein, CD18, Lysyl oxidase, Cathepsin D, E-Cadherin, VE-Cadherin, Nidogen, Angiopoietin 1 and Thrombospondin 2, and the differential expression levels were validated by RT-PCR. The chitinase activity was significantly higher in the blood from patients with wear-particle induced prosthesis loosening (p=0.001). However, using chitinase activity as a marker for early diagnosis, it has a specificity of 83% and a sensitivity of only 52%, due to a high variability both in the disease and in the control group. Experiment Overall Design: Gene expression profiles were generated from 5 periprosthetic membranes of wear-particle induced and 5 of infectious (septic) type using Affymetrix HG U133A oligonucleotide microarrays. The results of selected differentially expressed genes were validated by RT-PCR (n=30). The enzyme activity and the genotype of chitinase-1 were assessed in serum samples from 313 consecutive patients hospitalized for endoprosthesis loosening (n=54) or for other reasons, serving as control subjects (n=259).

ORGANISM(S): Homo sapiens

SUBMITTER: Lars Morawietz

PROVIDER: E-GEOD-7103 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Gene expression in endoprosthesis loosening: chitinase activity for early diagnosis?

Morawietz L L Weimann A A Schroeder J H JH Kuban R J RJ Ungethuem U U Kaps C C Slevogt H H Gehrke T T Krukemeyer M G MG Krenn V V

Journal of orthopaedic research : official publication of the Orthopaedic Research Society 20080301 3

The aim of the study was to identify markers for the early diagnosis of endoprosthesis loosening, for the differentiation between wear particle-induced and septic loosening and to gather new insights into the pathogenesis of endoprosthesis loosening. Gene expression profiles were generated from five periprosthetic membranes of wear particle-induced and five of infectious (septic) type using Affymetrix HG U133A oligonucleotide microarrays. The results of selected differentially expressed genes we ...[more]

PMID: 17902171

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Project description:Aims: We investigate sex differences and the role of oestrogen receptor beta (ERbeta) in a mouse model of pressure overload-induced myocardial hypertrophy. Methods and results: We performed transverse aortic constriction (TAC) or sham surgery in male and female wild-type (WT) and ER knockout (ERbeta-/-) C57Bl6 mice. All mice were characterised by echocardiography and haemodynamic measurements and were sacrificed nine weeks after surgery. Left ventricular (LV) samples were analysed by microarray profiling, real-time RT-PCR and histology. After nine weeks, WT males showed more hypertrophy and heart failure signs than WT females. Notably, WT females developed a concentric form of hypertrophy, while males developed eccentric hypertrophy. These sex differences were abolished in ERbeta-/- mice. ERbeta deletion augmented the TAC-induced increase in cardiomyocyte diameter in both sexes. Gene expression profiling revealed that male WT hearts had a stronger induction of matrix-related genes and a stronger repression of mitochondrial genes than female hearts. ERbeta-/- mice exhibited a different transcriptome. Induction of pro-apoptotic genes after TAC occurred in ERbeta-/- mice of both sexes with a stronger expression in ERbeta-/- males. Histological analysis revealed, that cardiac fibrosis was more pronounced in male WT TAC than in female mice. This was abolished in ERbeta-/- mice. Apoptosis was significantly induced in both sexes of ERbeta-/- TAC mice, but it was most prominent in males. Conclusion: Female sex offers protection against ventricular chamber dilation in the TAC model. Both the female sex and ER attenuate the development of fibrosis and apoptosis; thus slowing the progression to heart failure. The influence of sex (male/female) and estrogen receptor beta expression (ERbeta knockout/wildtype) on cardiac hypertrophy (transverse aortic constriction/sham operated) was investigated. The left ventricular transcriptome of four individual mice for each combination of the three factors (sex, genotype, surgery) was detected with Affymetrix RAE 430 2.0 GeneChip arrays.

Dataset Information

Transcription profiling of human samples to identify markers for early diagnosis of of endoprosthesis loosening

Publications

Gene expression in endoprosthesis loosening: chitinase activity for early diagnosis?

Similar Datasets

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