Detection of significant pathways in osteoporosis based on graph clustering

Xiao, Haijun; Shan, Liancheng; Zhu, Haiming; Xue, Feng

doi:10.3892/mmr.2012.1082

Cited by 14 publications

(13 citation statements)

References 55 publications

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“…3,16 In the present study, we also show a significant increase in CMPK2, a gene involved in the activation and differentiation of monocytes and macrophages. 49,50 SIGLEC1, a lectin expressed on monocytes following TLR-9 stimulation, 51 was also up-regulated in our study. The functional role of SIGLEC1 is not entirely clear; however, it has been shown to bind to CD43 on activated T cells.…”

Section: Discussionsupporting

confidence: 71%

Transcriptional profile in afferent lymph cells following vaccination with liposomes incorporating CpG

Neeland

Elhay²,

Powell

et al. 2015

Immunology

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SummaryVaccine formulations incorporating innate immune stimulants are highly immunogenic; however, the biological signals that originate in the peripheral tissues at the site of injection and are transmitted to the local lymph node to induce immunity remain unclear. By directly cannulating the ovine afferent lymphatic vessels, we have previously shown that it takes 72 hr for mature antigen-loaded dendritic cells and monocytes to appear within afferent lymph following injection of a liposomal formulation containing the Toll-like receptor ligand CpG. In this present study, we characterize the global transcriptional signatures at this time-point in ovine afferent lymph cells as they migrate from the injection site into the lymphatics following vaccination with a liposome antigen formulation incorporating CpG. We show that at 72 hr post vaccination, liposomes alone induce no changes in gene expression and inflammatory profiles within afferent lymph; however, the incorporation of CpG drives interferon, antiviral and cytotoxic gene programmes. This study also measures the expression of key genes within individual cell types in afferent lymph. Antiviral gene signatures are most prominent in lymphocytes, which may play a significant and unexpected role in sustaining the immune response to vaccination at the site of injection. These findings provide a comprehensive analysis of the in vivo immunological pathways that connect the injection site with the local draining lymph node following vaccination.

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Section: Discussionsupporting

confidence: 71%

Transcriptional profile in afferent lymph cells following vaccination with liposomes incorporating CpG

Neeland

Elhay²,

Powell

et al. 2015

Immunology

View full text Add to dashboard Cite

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“…This gene has been recently highlighted as potentially relevant for osteoporosis on the basis of a bioinformatics pathway analysis approach [39]. Imprinting of this gene appears to play a role in fetal growth, including fetal bone growth, birth weight and bone mass in childhood [40], [41], [42], [43].…”

Section: Resultsmentioning

confidence: 99%

Meta-Analysis of Genome-Wide Association Studies Identifies Six New Loci for Serum Calcium Concentrations

et al. 2013

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Calcium is vital to the normal functioning of multiple organ systems and its serum concentration is tightly regulated. Apart from CASR, the genes associated with serum calcium are largely unknown. We conducted a genome-wide association meta-analysis of 39,400 individuals from 17 population-based cohorts and investigated the 14 most strongly associated loci in ≤21,679 additional individuals. Seven loci (six new regions) in association with serum calcium were identified and replicated. Rs1570669 near CYP24A1 (P = 9.1E-12), rs10491003 upstream of GATA3 (P = 4.8E-09) and rs7481584 in CARS (P = 1.2E-10) implicate regions involved in Mendelian calcemic disorders: Rs1550532 in DGKD (P = 8.2E-11), also associated with bone density, and rs7336933 near DGKH/KIAA0564 (P = 9.1E-10) are near genes that encode distinct isoforms of diacylglycerol kinase. Rs780094 is in GCKR. We characterized the expression of these genes in gut, kidney, and bone, and demonstrate modulation of gene expression in bone in response to dietary calcium in mice. Our results shed new light on the genetics of calcium homeostasis.

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“…We found no reports of a role in bone, but it is involved in blood cell glycolysis. The gene that was not at the locus on chromosome 1 was DExD/H-box helicase 60 (DDX60) and is principally recognised as an RNA binding molecule with anti-viral properties, but it has also been mentioned as a potential candidate for osteoporosis in a study on human monocytes [51].…”

Section: Discussionmentioning

confidence: 99%

An eQTL in the cystathionine beta synthase gene is linked to osteoporosis in laying hens

et al. 2020

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Background: Skeletal damage is a challenge for laying hens because the physiological adaptations required for egg laying make them susceptible to osteoporosis. Previously, we showed that genetic factors explain 40% of the variation in end of lay bone quality and we detected a quantitative trait locus (QTL) of large effect on chicken chromosome 1. The aim of this study was to combine data from the commercial founder White Leghorn population and the F2 mapping population to fine-map this QTL and understand its function in terms of gene expression and physiology. Results: Several single nucleotide polymorphisms on chromosome 1 between 104 and 110 Mb (galGal6) had highly significant associations with tibial breaking strength. The alternative genotypes of markers of large effect that flanked the region had tibial breaking strengths of 200.4 vs. 218.1 Newton (P < 0.002) and, in a subsequent founder generation, the higher breaking strength genotype was again associated with higher breaking strength. In a subsequent generation, cortical bone density and volume were increased in individuals with the better bone genotype but with significantly reduced medullary bone quality. The effects on cortical bone density were confirmed in a further generation and was accompanied by increased mineral maturity of the cortical bone as measured by infrared spectrometry and there was evidence of better collagen cross-linking in the cortical bone. Comparing the transcriptome of the tibia from individuals with good or poor bone quality genotypes indicated four differentially-expressed genes at the locus, one gene, cystathionine beta synthase (CBS), having a nine-fold higher expression in the genotype for low bone quality. The mechanism was cis-acting and although there was an amino-acid difference in the CBS protein between the genotypes, there was no difference in the activity of the enzyme. Plasma homocysteine concentration, the substrate of CBS, was higher in the poor bone quality genotype. Conclusions: Validated markers that predict bone strength have been defined for selective breeding and a gene was identified that may suggest alternative ways to improve bone health in addition to genetic selection. The identification of how genetic variants affect different aspects of bone turnover shows potential for translational medicine.

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Detection of significant pathways in osteoporosis based on graph clustering

Cited by 14 publications

References 55 publications

Transcriptional profile in afferent lymph cells following vaccination with liposomes incorporating CpG

Transcriptional profile in afferent lymph cells following vaccination with liposomes incorporating CpG

Meta-Analysis of Genome-Wide Association Studies Identifies Six New Loci for Serum Calcium Concentrations

An eQTL in the cystathionine beta synthase gene is linked to osteoporosis in laying hens

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