Aspasia Tsezou

University of Thessaly, Iolcus, Thessaly, Greece

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Publications (121)468.99 Total impact

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    ABSTRACT: Several studies have shown that osteoarthritis (OA) is strongly associated with metabolic related disorders, highlighting OA as the fifth component of the Metabolic Syndrome (MetS). Based on our previous findings on dysregulation of cholesterol homeostasis in OA, we were prompted to investigate whether microRNA-33a (miR-33a), one of the master regulators of cholesterol and fatty acid metabolism, plays a key role in OA pathogenesis. Articular cartilage samples were obtained from 14 patients with primary OA undergoing total knee replacement surgery. Normal cartilage was obtained from 9 individuals undergoing fracture repair surgery. Bioinformatics was used to identify miR-33a target genes. MiR-33a and sterol regulatory element binding protein 2 (SREBP-2) expression levels were investigated using real-time PCR and their expression was also assessed after treatment with transforming growth factor-beta1 (TGF-beta1) in cultured chondrocytes. Investigation of Akt phosphorylation after treatment with both TGF-beta1 and miR-33a inhibitor or TGF-beta1 and miR-33a mimic was assessed by western blot analysis. Furthermore, we evaluated the effect of miR-33a mimic and miR-33a inhibitor on Smad7, a negative regulator of TGF-beta signaling, on cholesterol efflux related genes, ATP-binding-cassette transporter A1 (ABCA1), Apolipoprotein A1 (ApoA1), liver X receptors (LXRalpha and LXRbeta), as well as on matrix metalloproteinase-13 (MMP-13) using real time PCR. We found that the expression of miR-33a and its host gene SREBP-2 was significantly elevated in OA chondrocytes compared to normal. Treatment of cultured chondrocytes with TGF-beta1 resulted in increased expression of both miR-33a and SREBP-2, and in rapid induction of Akt phosphorylation, while TGF-beta-induced Akt phosphorylation was enhanced by miR-33a and suppressed by inhibition of miR-33a, as a possible consequence of Smad7 regulation by miR-33a. Moreover, treatment of normal chondrocytes with miR-33a resulted in significantly reduced ABCA1 and ApoA1 mRNA expression levels and significantly elevated MMP-13 expression levels, promoting the OA phenotype, while miR-33a's suppressive effect was reversed using its inhibitor. Our findings suggest, for the first time to our knowledge, that miR-33a regulates cholesterol synthesis through the TGF-beta1/Akt/SREBP-2 pathway, and cholesterol efflux related genes ABCA1 and ApoA1 in OA chondrocytes, pointing to its identification as a novel target for ameliorating the OA phenotype.
    Arthritis research & therapy 12/2015; 17(1):556. DOI:10.1186/s13075-015-0556-y · 4.12 Impact Factor
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    ABSTRACT: Background Osteoarthritis (OA) is a multi-factorial disease leading progressively to loss of articular cartilage and subsequently to loss of joint function. While hypertrophy of chondrocytes is a physiological process implicated in the longitudinal growth of long bones, hypertrophy-like alterations in chondrocytes play a major role in OA. We performed a quantitative proteomic analysis in osteoarthritic and normal chondrocytes followed by functional analyses to investigate proteome changes and molecular pathways involved in OA pathogenesis. Methods Chondrocytes were isolated from articular cartilage of ten patients with primary OA undergoing knee replacement surgery and six normal donors undergoing fracture repair surgery without history of joint disease and no OA clinical manifestations. We analyzed the proteome of chondrocytes using high resolution mass spectrometry and quantified it by label-free quantification and western blot analysis. We also used WebGestalt, a web-based enrichment tool for the functional annotation and pathway analysis of the differentially synthesized proteins, using the Wikipathways database. ClueGO, a Cytoscape plug-in, is also used to compare groups of proteins and to visualize the functionally organized Gene Ontology (GO) terms and pathways in the form of dynamical network structures. Results The proteomic analysis led to the identification of a total of ~2400 proteins. 269 of them showed differential synthesis levels between the two groups. Using functional annotation, we found that proteins belonging to pathways associated with regulation of the actin cytoskeleton, EGF/EGFR, TGF-β, MAPK signaling, integrin-mediated cell adhesion, and lipid metabolism were significantly enriched in the OA samples (p ≤10−5). We also observed that the proteins GSTP1, PLS3, MYOF, HSD17B12, PRDX2, APCS, PLA2G2A SERPINH1/HSP47 and MVP, show distinct synthesis levels, characteristic for OA or control chondrocytes. Conclusion In this study we compared the quantitative changes in proteins synthesized in osteoarthritic compared to normal chondrocytes. We identified several pathways and proteins to be associated with OA chondrocytes. This study provides evidence for further testing on the molecular mechanism of the disease and also propose proteins as candidate markers of OA chondrocyte phenotype.
    Clinical Proteomics 04/2015; 12(1-1). DOI:10.1186/s12014-015-9085-6
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    ABSTRACT: Telomere shortening to a critical limit is associated with replicative senescence. This process is prevented by the enzyme telomerase. Oxidative stress and chronic inflammation are factors accelerating telomere loss. Chronic hemodialysis, typically accompanied by oxidative stress and inflammation, may be also associated with replicative senescence. To test this hypothesis, we determined telomere length and telomerase activity in peripheral blood mononuclear cells (PBMCs) in a cross-sectional study. Hemodialysis patients at the University Hospital Larissa and healthy controls were studied. Telomere length was determined by the TeloTAGGG Telomere Length Assay and telomerase activity by Telomerase PCR-ELISA (Roche Diagnostics GmbH, Mannheim, Germany). We enrolled 43 hemodialysis patients (17 females; age 65.0 ± 12.7 years) and 23 controls (six females; age 62.1 ± 15.7 years). Between the two groups, there was no difference in telomere length (6.95 ± 3.25 vs. 7.31 ± 1.96 kb; P = 0.244) or in telomerase activity (1.82 ± 2.91 vs. 2.71 ± 3.0; P = 0.085). Telomere length correlated inversely with vintage of hemodialysis (r = -0.332, P = 0.030). In hemodialysis patients, positive telomerase activity correlated with telomere length (r = 0.443, P = 0.030). Only age, and neither telomere length nor telomerase activity, was an independent survival predictor (hazard ratio 1.116, 95% confidence interval 1.009-1.234, P = 0.033). In this study, telomere length and telomerase activity in PBMCs are not altered in hemodialysis patients compared with healthy controls. Long duration of hemodialysis treatment is associated with telomere shortening and positive telomerase activity with an increased telomere length in PBMCs of hemodialysis patients. The underlying mechanism and clinical implications of our findings require further investigation. Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.
    Artificial Organs 04/2015; DOI:10.1111/aor.12453 · 1.87 Impact Factor
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    ABSTRACT: Metastasis, responsible for most deaths from breast cancer (BC), is a multistep process leading to cancer cell spread. Extracellular matrix (ECM)-related adhesion and apoptosis resistance play pivotal role in metastasis. Ras suppressor-1 (RSU-1) localizes to cell-ECM adhesions and binds to pro-survival adhesion protein PINCH-1. Little is known about the role of RSU-1 in BC. In the present study, we investigated the role of RSU-1 in BC metastasis using two BC cell lines that differ in terms of their metastatic potential and a set of 32 human BC samples from patients with or without lymph node metastasis. We show that RSU-1 is upregulated in the aggressive MDA-MB-231 cells compared to MCF-7 and that its silencing by siRNA leads to upregulation of PINCH-1, induction of proliferation and reduction of apoptosis through downregulation of the pro-apoptotic gene p53-upregulated-modulator-of-apoptosis (PUMA). Our findings in the cell lines were further validated in the human BC tissues where normal adjacent tissues were used as controls. We demonstrate for the first time, that RSU-1 expression is upregulated in metastatic BC samples and downregulated in non-metastatic while it is negatively correlated with PINCH-1 and positively correlated with PUMA expression, suggesting that a pro-apoptotic mechanism is in place in metastatic BC samples and identifying RSU-1 as a potentially interesting molecule that needs to be evaluated further as a novel BC metastasis biomarker.
    Clinical and Experimental Metastasis 02/2015; 32(3). DOI:10.1007/s10585-015-9701-x · 3.73 Impact Factor
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    ABSTRACT: Tamoxifen is a major treatment modality for estrogen receptor positive breast cancer, but the occurrence of resistance remains a problem. Recently, obesity-related leptin has been found to interfere with tamoxifen in breast cancer MCF-7 cells. In the present study we investigated the effect of leptin on three tamoxifen-treated breast cancer cell types (i.e., MDA-MB-231, MCF-7 and MCF-7/HER2). The effect of tamoxifen/leptin treatment was evaluated using a MTT cell viability assay. mRNA expression was assessed by real time PCR and protein expression by Western blotting. WWOX, Survivin and BCL2 gene promoter activities were evaluated by chromatin immunoprecipitation. Cell viability assays revealed that estrogen receptor negative MDA-MB-231 cells were resistant, that estrogen receptor positive MCF-7 cells were HER2 cells were relatively resistant to/HER2 cells were relatively resistant to tamoxifen, while leptin co-administration 'rescued' MCF-7 and, especially, MCF-7/HER2 cells from the anti-proliferative effect of tamoxifen. The cell lines also exhibited a different phosphorylation status of STAT3, a transcription factor that is activated by the obesity related leptin receptor b (Ob-Rb). Most importantly, chromatin immunoprecipitation assays revealed differential STAT3 binding to the anti-apoptotic BCL2 and pro-apoptotic WWOX gene promoters in MCF-7 and MCF-7/HER2 cells, leading to concomitant modifications of its mRNA/protein expression levels, thus providing a selective advantage to HER2 over-expressing MCF-7/HER2 cells after treatment with tamoxifen and tamoxifen plus leptin. Our study provides novel evidence indicating that synergy between the leptin/Ob-Rb/STAT3 signalling pathway and the HER2 receptor protects tamoxifen-treated HER2 over-expressing cells from the inhibitory effect of tamoxifen through differential regulation of apoptosis-related genes.
    Cellular Oncology 12/2014; 38(2). DOI:10.1007/s13402-014-0213-5 · 2.12 Impact Factor
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    ABSTRACT: The widespread use of pesticides substances nowadays largely guarantees the protection of crops and people from undesired pests. However, exposure to pesticides was related to a variety of human health effects. The present study was conducted in the region of Thessaly which is characterized by intensive agricultural activities and wide use of pesticides. The study aimed at estimating the oxidative damage to DNA in different subpopulations in Thessaly region (Greece) and investigating its correlation with exposure to pesticides and other potential risk factors. In total, the study involved 80 pesticide sprayers, 85 rural residents and 121 individuals, inhabitants of the city of Larissa. Demographic characteristics, habits, medical history and exposure history of the participants to pesticides were recorded by personal interviews. Blood and urine samples were collected from all participants. For the measurement of exposure to organophosphorus insecticides, dialkylphosphate (DAP) metabolites were quantified in urine, by gas chromatography-mass spectrometry. Genomic DNA was extracted from peripheral blood samples and the oxidation by-product 8-hydroxydeoxyguanosine (8-OHdG) was determined by Enzyme Immuno-Assay. Urinary metabolite concentrations were not associated with 8-OHdG levels but it was found that pesticide sprayers had significantly higher levels of 8-OHdG (p = 0.007) in comparison to the control group. Last season's exposure to insecticides and fungicides, expressed as total area treated multiplied by the number of applications, showed a statistically significant association with the risk of having high 8-OHdG levels [RR: 2.19 (95%CI:1.09-4.38) and RR: 2.32 (95% CI:1.16-4.64) respectively]. Additionally, from the subgroups of pesticides examined, seasonal exposure to neonicotinoid insecticides [RR: 2.22 (95% CI:1.07-4.63)] and glufosinate ammonium [RR: 3.26 (95% CI:1.38-7.69)] was found to have the greater impact on 8-OHdG levels.
    Science of The Total Environment 10/2014; 496:358–364. DOI:10.1016/j.scitotenv.2014.07.062 · 3.16 Impact Factor
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    ABSTRACT: Background The purpose of this study was to investigate plasma homocysteine levels and polymorphisms in genes encoding enzymes in the metabolic pathway of homocysteine in association with primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PXFG). Methods A total of 156 glaucoma patients (76 with POAG and 80 with PXFG) and 135 controls matched for age and sex were enrolled in this study. Plasma homocysteine levels were measured using a commercially available enzyme-linked immunosorbent assay kit. DNA was extracted from peripheral blood leukocytes and real-time polymerase chain reaction was performed for genotyping of the samples. Patients were genotyped using predesigned TaqMan® single nucleotide polymorphism genotyping assays for two exon variations (rs1801131, rs1801133) in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene and one intron variation (rs8006686) in the methylenetetrahydrofolate dehydrogenase (MTHFD1) gene. Results Homocysteine levels were slightly higher in the patient group (POAG and PXFG) compared with controls, but the difference did not reach statistical significance. The minor alleles of the MTHFR single nucleotide polymorphisms showed a protective effect for POAG and showed an increased risk for PXFG, but none of these associations reached statistical significance (P>0.05). The minor allele of MTHFD1 rs8006686 showed a trend for increased risk of both POAG and PXFG (P>0.05). No statistically significant interaction was seen between the genetic variants and homocysteine levels (P>0.05). Conclusion Our results show that neither the examined single nucleotide polymorphisms from genes involved in the pathway of homocysteine metabolism nor the measured homocysteine levels were associated with POAG or PXFG in our study cohort.
    Clinical ophthalmology (Auckland, N.Z.) 09/2014; 8:1819-25. DOI:10.2147/OPTH.S64904
  • Osteoarthritis and Cartilage 04/2014; 22:S146. DOI:10.1016/j.joca.2014.02.270 · 4.66 Impact Factor
  • Osteoarthritis and Cartilage 04/2014; 22:S232-S233. DOI:10.1016/j.joca.2014.02.448 · 4.66 Impact Factor
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    ABSTRACT: To assess candidate genes for association with osteoarthritis (OA) and identify promising genetic factors and, secondarily, to assess the candidate gene approach in OA. A total of 199 candidate genes for association with OA were identified using Human Genome Epidemiology (HuGE) Navigator. All of their single-nucleotide polymorphisms (SNPs) with an allele frequency of >5% were assessed by fixed-effects meta-analysis of 9 genome-wide association studies (GWAS) that included 5,636 patients with knee OA and 16,972 control subjects and 4,349 patients with hip OA and 17,836 control subjects of European ancestry. An additional 5,921 individuals were genotyped for significantly associated SNPs in the meta-analysis. After correction for the number of independent tests, P values less than 1.58 × 10(-5) were considered significant. SNPs at only 2 of the 199 candidate genes (COL11A1 and VEGF) were associated with OA in the meta-analysis. Two SNPs in COL11A1 showed association with hip OA in the combined analysis: rs4907986 (P = 1.29 × 10(-5) , odds ratio [OR] 1.12, 95% confidence interval [95% CI] 1.06-1.17) and rs1241164 (P = 1.47 × 10(-5) , OR 0.82, 95% CI 0.74-0.89). The sex-stratified analysis also showed association of COL11A1 SNP rs4908291 in women (P = 1.29 × 10(-5) , OR 0.87, 95% CI 0.82-0.92); this SNP showed linkage disequilibrium with rs4907986. A single SNP of VEGF, rs833058, showed association with hip OA in men (P = 1.35 × 10(-5) , OR 0.85, 95% CI 0.79-0.91). After additional samples were genotyped, association at one of the COL11A1 signals was reinforced, whereas association at VEGF was slightly weakened. Two candidate genes, COL11A1 and VEGF, were significantly associated with OA in this focused meta-analysis. The remaining candidate genes were not associated.
    04/2014; 66(4):940-9. DOI:10.1002/art.38300
  • Annals of the Rheumatic Diseases 01/2014; 71(Suppl 3):473-474. DOI:10.1136/annrheumdis-2012-eular.2957 · 9.27 Impact Factor
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    ABSTRACT: Glucuronidation, mediated by the UDP-glucuronosyltransferase 1A1 (UGT1A1) enzyme, is an important metabolic process during which steroids are converted to more easily excreted compounds in steroid target tissues, such as the prostate. The aim of our study was to investigate the possible correlation between UGT1A1 promoter gene polymorphism and benign prostatic hyperplasia. 421 blood samples were obtained from 138 consecutive patients diagnosed with benign prostatic hypeplasia (BPH group) and 283 healthy volunteers (control group). A(TA)6TAA promoter polymorphism of UGT1A1 gene was studied using the Fragment Analysis Software of an automated DNA sequencer and three genotypes (homozygous 7/7, heterozygous 6/7 and normal homozygous 6/6) were identified. No significant differences were observed between the BPH group and controls regarding the genotyping distribution of the three UGT1A1 promoter genotypes (P = 0.39). Also, no association was found between overall disease risk and the presence of the polymorphic homozygous genotype (TA(7)/TA)7) vs. TA(6)/TA(7) + TA(6)/TA(6)) (P = 0.31). Our data suggest that the TA repeat polymorphism of UGT1A1 is not associated with increased BPH risk susceptibility in Caucasian men.
    Molecular Biology Reports 09/2013; 40(12). DOI:10.1007/s11033-013-2781-2 · 1.96 Impact Factor
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    ABSTRACT: Osteoarthritis (OA) is the most common form of arthritis with a clear genetic component. To identify novel loci associated with hip OA we performed a meta-analysis of genome-wide association studies (GWAS) on European subjects. We performed a two-stage meta-analysis on more than 78 000 participants. In stage 1, we synthesised data from eight GWAS whereas data from 10 centres were used for 'in silico' or 'de novo' replication. Besides the main analysis, a stratified by sex analysis was performed to detect possible sex-specific signals. Meta-analysis was performed using inverse-variance fixed effects models. A random effects approach was also used. We accumulated 11 277 cases of radiographic and symptomatic hip OA. We prioritised eight single nucleotide polymorphism (SNPs) for follow-up in the discovery stage (4349 OA cases); five from the combined analysis, two male specific and one female specific. One locus, at 20q13, represented by rs6094710 (minor allele frequency (MAF) 4%) near the NCOA3 (nuclear receptor coactivator 3) gene, reached genome-wide significance level with p=7.9×10(-9) and OR=1.28 (95% CI 1.18 to 1.39) in the combined analysis of discovery (p=5.6×10(-8)) and follow-up studies (p=7.3×10(-4)). We showed that this gene is expressed in articular cartilage and its expression was significantly reduced in OA-affected cartilage. Moreover, two loci remained suggestive associated; rs5009270 at 7q31 (MAF 30%, p=9.9×10(-7), OR=1.10) and rs3757837 at 7p13 (MAF 6%, p=2.2×10(-6), OR=1.27 in male specific analysis). Novel genetic loci for hip OA were found in this meta-analysis of GWAS.
    Annals of the rheumatic diseases 08/2013; DOI:10.1136/annrheumdis-2012-203114 · 9.27 Impact Factor
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    ABSTRACT: Cell adhesion proteins that connect each cell to neighboring cells and the extracellular matrix play a fundamental role in metastasis. Mitogen-inducible gene-2 (MIG2), is a cell-matrix adhesion protein, which through migfilin, interacts with filamin-A, being linked to actin cytoskeleton. Aim: Recent studies have implicated both MIG2 and migfilin in cancer, but little is known regarding their expression in breast cancer. In this study, we investigated this topic. mRNA and protein expression was examined in 30 breast cancer samples and compared to that of normal adjacent tissue using real time-polymerase chain reaction (PCR) and western blotting. Our results showed that expression of MIG2 and migfilin was significantly reduced in the majority of the breast cancer tissues compared to normal tissues regardless of metastatic status and disease stage. Both MIG2 and migfilin are down-regulated in breast cancer.
    Anticancer research 05/2013; 33(5):1977-81. · 1.87 Impact Factor
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    ABSTRACT: Fibroblast growth factor 23 (FGF-23) is a bone-derived circulating phosphaturic factor that decreases serum concentration of phosphate and vitamin D, suggested to actively participate in a complex renal-gastrointestinal-skeletal axis. Serum FGF-23 concentrations, as well as various other laboratory parameters involved in bone homeostasis, were measured and analyzed with regard to various diseases and patients' characteristics in 44 patients with Crohn disease (CD) and 20 healthy controls (HCs) included in this cross-sectional study. Serum FGF-23 levels were significantly lower in patients with CD (900.42 ± 815.85pg/mL) compared with HC (1410.94 ± 1000.53pg/mL), p = 0.037. Further analyses suggested FGF-23 as a factor independent from various parameters including age (r = -0.218), body mass index (r = -0.115), 25-hydroxy vitamin D (r = 0.126), parathyroid hormone (r = 0.084), and bone mineral density (BMD) of hip and lumbar (r = 0.205 and r = 0.149, respectively). This observation remained even after multivariate analyses, exhibiting that BMD was not affected by FGF-23, although parameters such as age (p = 0.026), cumulative prednisolone dose (p < 0.0001), and smoking status (p = 0.024) were strong determinants of BMD regarding hip. Lower FGF-23 levels in patients with bowel inflammation are accompanied but not directly correlated with lower vitamin D levels, showing no impact on BMD determination of young adults with CD. The downregulation of serum FGF-23 levels in CD appears as a secondary compensatory effect on the bone and mineral metabolism induced by chronic intestinal inflammation.
    Journal of Clinical Densitometry 04/2013; 17(1). DOI:10.1016/j.jocd.2013.03.019 · 1.60 Impact Factor
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    ABSTRACT: Osteoarthritis (OA) is a debilitating disease of the joints characterized by cartilage degradation but to date there is no available pharmacological treatment to inhibit disease progression neither is there any available biomarker to predict its development. In the present study, we examined the expression level and possible involvement of novel cell-ECM adhesion-related molecules such as Iintegrin Linked Kinase (ILK), PINCH, parvin, Mig-2 and Migfilin in OA pathogenesis using primary human articular chondrocytes from healthy individuals and OA patients. Our findings show that only ILK and Migfilin were upregulated in OA compared to the normal chondrocytes. Interestingly, Migfilin silencing in OA chondrocytes rather exacerbated than ameliorated the osteoarthritic phenotype, as it resulted in even higher levels of catabolic and hypertrophic markers while at the same time induced reduction in ECM molecules such as aggrecan. Furthermore, we also provide a link between Migfilin and β-catenin activation in OA chondrocytes, showing Migfilin to be inversely correlated with β-catenin. Thus, the present study emphasizes for the first time to our knowledge the role of Migfilin in OA and highlights the importance of cell-ECM adhesion proteins in OA pathogenesis.
    Biochemical and Biophysical Research Communications 12/2012; 430(2). DOI:10.1016/j.bbrc.2012.12.008 · 2.28 Impact Factor
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    ABSTRACT: INTRODUCTION: We aimed to explore the involvement of a multiallelic functional polymorphism in knee osteoarthritis (OA) susceptibility as a prototype of possible genetic factors escaping GWAS detection. METHODS: OA patients and controls from three European populations (Greece, Spain and the UK) adding up to 1003 patients (716 women, 287 men) that had undergone total knee joint replacement (TKR) due to severe primary OA and 1543 controls (758 women, 785 men) lacking clinical signs or symptoms of OA were genotyped for the D6S1276 microsatellite in intron 1 of BMP5. Genotype and mutiallelic trend tests were used to compare cases and controls. RESULTS: Significant association was found between the microsatellite and knee OA in women (P from 3.1 x10-4 to 4.1 x10-4 depending on the test), but not in men. Three of the alleles showed significant differences between patients and controls, one of them of increased risk and two of protection. The gender association and the allele direction of change were very concordant with the previously reported for hip OA. CONCLUSIONS: We have found association of knee OA in women with the D6S1276 functional microsatellite that modifies in cis the expression of BMP5 making this a sounder OA genetic factor and extending its involvement to other joint. This result also shows the interest of analysing other multiallelic polymorphisms.
    Arthritis research & therapy 11/2012; 14(6):R257. DOI:10.1186/ar4102 · 4.12 Impact Factor
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    ABSTRACT: BACKROUND: A case control study to evaluate whether a single serum measurement of Angiopoietin-1 (ANG-1) and Angiopoietin-2 (ANG-2) at 6-8weeks gestation can differentiate failed pregnancies, whether ectopic pregnancies (EP) or missed abortions (MA), from healthy intrauterine pregnancies (IUP). INTERVENTION(S): Serum and tissue mRNA determination of ANG-1 and ANG-2 levels by ELISA and RTPCR,from 60 (30 EP, 30 MA) patients with failed early pregnancy and 33 IUPs. RESULTS: ANG-1 and ANG-2 concentrations and their ratio are lower in EP (median, 689 and 302pg/ml, respectively) and MA cases (median, 810 and 402pg/ml, respectively) compared to IUP (median, 963 and 1477pg/ml, respectively) (p<0.05, for all). Unlike ANG-2, serum ANG- 1 discriminates an EP from a MA (p=0.011). Trophoblastic ANG-1 mRNA expression levels are lower in EP compared to MA and IUP (p<0.05), while ANG-2 mRNA is higher in EP and MA than in IUP (p<0.05). CONCLUSIONS: A single measurement of serum ANG-1 and ANG-2 at 6-8weeks of gestation designate the outcome of a pregnancy, as their levels are significantly decreased in failed than normal pregnancies. Serum ANG-1 showed potential to discriminate MA from EP.
    Clinica chimica acta; international journal of clinical chemistry 10/2012; 415. DOI:10.1016/j.cca.2012.10.031 · 2.76 Impact Factor
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    ABSTRACT: Clinical and molecular description of a fetus in prenatal diagnosis with a rare de novo ring 10 and deletions of 12.59 Mb in 10p15.3ep14 and 4.22 Mb in 10q26.3 a b s t r a c t Ring chromosomes are rare cytogenetic findings and are mostly associated with an abnormal phenotype. We report on the prenatal diagnosis of a ring chromosome 10 in a fetus in which talipes equinovarus was incidentally found during routine obstetric ultrasound at 22 weeks of gestation. Amniocentesis was undertaken and cytogenetic analysis revealed a de novo non-mosaic apparently stable ring chromosome 10 replacing one of the two homologs. Multiplex Ligation-dependent Probe Amplification (MLPA) revealed subtelomeric deletions in both the short and long arm of chromosome 10. Analysis with high resolution micro-array based comparative genomic hybridization (array-CGH), defined the ring chro-mosome as del 10p15.3ep14 (12.59 Mb in size) and del 10q26.3 (4.22 Mb in size) and revealed the genes that are deleted. After elected termination of the pregnancy at 27th week of gestation a detailed autopsy of the fetus allowed for genotypeephenotype correlations. To our knowledge, this is the first case of a de novo ring chromosome 10 which is reported during prenatal diagnosis and is thoroughly investigated with array CGH and autopsy study. Ó 2011 Elsevier Masson SAS. All rights reserved. 1. Methods of detection 1.1. Cytogenetics Chromosomal analyses were performed on amniotic fluid, parental peripheral blood, placenta and fetal skin using conven-tional GTG-banding techniques at the 550 band level. 1.2. Array-CGH Agilent Human Genome CGH 244K microarrays with an average spatial resolution of 12 kb were used in the study (Agilent Tech-nologies, Santa Clara, CA). Genomic DNA from the proband and pooled normal male reference DNA (Promega Corporation, Madi-son, WI) were digested with AluI and RsaI (Promega Corporation) and labeled with Agilent Genomic DNA labeling Kit according to manufacturer's instructions. Patient and reference DNA were labeled with Cy3 and Cy5, respectively and were co-hybridized to arrays for 40 h at 65 C in a rotating oven (Agilent Technologies) at 20 rpm. The arrays were then washed and scanned with an Agilent Microarray Scanner. Data were extracted using Feature Extraction 9.1 software (Agilent Technologies) and analyzed using CGH Analytics 3.4 software (Agilent Technologies). Genomic copy number changes were identified with the assistance of the Aber-ration Detection Method 1 algorithm with a threshold of 6. Centralization and fuzzy zero corrections were applied to remove putative variant intervals with small average log 2 ratios. For the location of genes in the deleted/duplicated genomic segments the) and the Ensemble Genome Browser (http://www.ensembl.org) were used. 1.3. Chromosomal anomalies The fetus presented with talipes equinovarus at 22 weeks of gestation during a routine scan and an amniocentesis was per-formed. Rapid QF-PCR (quantitative fluorescence PCR) results were consistent with euploidy for the chromosomes investigated (13, 18, 21, X and Y). Conventional cytogenetic analysis revealed a 46,XY,r(10) abnormal non-mosaic fetal karyotype with a ring
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    ABSTRACT: Osteoarthritis (OA) is a common disease with a genetic component for its etiology. Recently, a genetic association of a single nucleotide polymorphism (SNP), rs17039192 in HIF-2α with knee OA has been reported in a Japanese population; however, controversy exits for its replication and a role of HIF-2α in OA. This study aimed to evaluate the association of the SNP by a large-scale replication study. A total of 8,457 subjects (3,129 OA cases and 5,328 controls) from seven independent cohorts from six countries (Japan, China, Taiwan, Korea, Greece, and Australia) were recruited and genotyped. The association of rs17039192 with knee OA was evaluated by meta-analyses. The association of the HIF-2α SNP was not replicated in any of the populations. Contrary to the previous report, the odds ratios (ORs) of the risk allele frequency were all less than 1. A combined analysis for the seven populations also showed no replication of the association (OR = 0.91, 95% confidence interval = 0.81-1.03). Our large-scale meta-analysis showed that the association of rs17039192 in HIF-2α with knee OA is negative. The significance of HIF-2α in human OA (idiopathic OA as a common disease) should be further evaluated carefully.
    Journal of Orthopaedic Research 08/2012; 30(8):1244-8. DOI:10.1002/jor.22063 · 2.97 Impact Factor

Publication Stats

2k Citations
468.99 Total Impact Points

Institutions

  • 2006–2015
    • University of Thessaly
      • • School of Medicine
      • • Ορθοπεδική Κλινική
      Iolcus, Thessaly, Greece
    • Aghia Sophia Children’s Hospital
      Athínai, Attica, Greece
  • 2012
    • Center for Research and Technology, Thessaly
      Iolcus, Thessaly, Greece
  • 2011
    • Newcastle University
      • Institute of Cellular Medicine
      Newcastle upon Tyne, ENG, United Kingdom
  • 2010
    • Wellcome Trust Sanger Institute
      Cambridge, England, United Kingdom
    • Harvard Medical School
      • Department of Biological Chemistry and Molecular Pharmacology
      Boston, MA, United States
  • 2005–2008
    • General University Hospital of Larissa
      Lárissa, Thessaly, Greece
  • 1993–2000
    • Aglaia Kyriakou Children's Hospital
      Athínai, Attica, Greece