Browse
Submit Data
Databases
API
Help

Dataset Information

22 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The integrative analysis of DNA methylation and mRNA expression profiles confirmed the role of selenocompound metabolism pathway in Kashin-Beck disease.

ABSTRACT: Kashin-Beck disease (KBD) is an endemic chronic osteochondropathy. The etiology of KBD remains unknown. In this study, we conducted an integrative analysis of genome-wide DNA methylation and mRNA expression profiles between KBD and normal controls to identify novel candidate genes and pathways for KBD. Articular cartilage samples from 17 grade III KBD patients and 17 healthy controls were used in this study. DNA methylation profiling of knee cartilage and mRNA expression profile data were obtained from our previous studies. InCroMAP was performed to integrative analysis of genome-wide DNA methylation profiles and mRNA expression profiles. Gene ontology (GO) enrichment analysis was conducted by online DAVID 6.7. The quantitative real-time polymerase chain reaction (qPCR), Western blot, immunohistochemistry (IHC), and lentiviral vector transfection were used to validate one of the identified pathways. We identified 298 common genes (such as COL4A1, HOXA13, TNFAIP6 and TGFBI), 36 GO terms (including collagen function, skeletal system development, growth factor), and 32 KEGG pathways associated with KBD (including Selenocompound metabolism pathway, PI3K-Akt signaling pathway, and TGF-beta signaling pathway). Our results suggest the dysfunction of many genes and pathways implicated in the pathogenesis of KBD, most importantly, both the integrative analysis and in vitro study in KBD cartilage highlighted the importance of selenocompound metabolism pathway in the pathogenesis of KBD for the first time.

SUBMITTER: Li P

PROVIDER: S-EPMC7513840 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Integrating genome-wide DNA methylation and mRNA expression profiles identified different molecular features between Kashin-Beck disease and primary osteoarthritis.

Project description:BackgroundKashin-Beck disease (KBD) is an endemic osteochondropathy of unknown etiology. Osteoarthritis (OA) is a form of degenerative joint disease sharing similar clinical manifestations and pathological changes to articular cartilage with KBD.MethodsA genome-wide DNA methylation profile of articular cartilage from five KBD patients and five OA patients was first performed using the Illumina Infinium HumanMethylation450 BeadChip. Together with a previous gene expression profiling dataset comparing KBD cartilage with OA cartilage, an integrative pathway enrichment analysis of the genome-wide DNA methylation and the mRNA expression profiles conducted in articular cartilage was performed by InCroMAP software.ResultsWe identified 241 common genes altered in both the DNA methylation profile and the mRNA expression profile of articular cartilage of KBD versus OA, including CHST13 (NM_152889, fold-change = 0.5979, P methy = 0.0430), TGFBR1 (NM_004612, fold-change = 2.077, P methy = 0.0430), TGFBR2 (NM_001024847, fold-change = 1.543, P methy = 0.037), TGFBR3 (NM_001276, fold-change = 0.4515, P methy = 6.04 × 10-4), and ADAM12 (NM_021641, fold-change = 1.9768, P methy = 0.0178). Integrative pathway enrichment analysis identified 19 significant KEGG pathways, including mTOR signaling (P = 0.0301), glycosaminoglycan biosynthesis-chondroitin sulfate/dermatan sulfate (P = 0.0391), glycosaminoglycan biosynthesis-keratan sulfate (P = 0.0278), and PI3K-Akt signaling (P = 0.0243).ConclusionThis study identified different molecular features between Kashin-Beck disease and primary osteoarthritis and provided novel clues for clarifying the pathogenetic differences between KBD and OA.

| S-EPMC5842623 | biostudies-literature

Integrative Analysis of Genome-Wide Association Studies and DNA Methylation Profile Identified Genetic Control Genes of DNA Methylation for Kashin-Beck Disease.

Project description:ObjectiveEpigenetic modifications of DNA are regarded as a crucial factor for understanding the molecular basis of complex phenotypes. This study aims to uncover insight into the epigenetic modifications for Kashin-Beck disease (KBD) by integrating genome-wide association studies (GWAS), methylation quantitative trait loci (meQTLs), and DNA methylation profiles data.DesignThe knee articular cartilages of 5 KBD patients and 5 healthy controls were collected for DNA methylation profiling, using Illumina Infinium HumanMethylation450 BeadChip. Mass spectrograph validation of identified differently methylated genes was conducted using independent samples of 4 KBD patients and 3 healthy controls, together with a previous sample of 2743 Han Chinese individuals of GWAS study for KBD and a study of 697 normal subjects for meQTLs annotation datasets. KBD GWAS single nucleotide polymorphisms (SNPs) and normal meQTLs SNPs were integrated with DNA methylation profiles of KBD articular cartilage to identify genetic control (GC) genes of DNA methylation for KBD. Quantitative polymerase chain reaction (qPCR) was performed to validate the mRNA expression of several identified candidate genes.ResultsA total of 162 CpG sites, 253 SNPs, and 123 GC genes for KBD were identified. Enrichment analysis detected 642 marked GO terms and 19 KEGG pathways (P < 0.05). Six potential key GC genes were conducted for qPCR experiment (ERG, MN1, MITF, WISP1, TRIO, and NOSTRIN).ConclusionsThe results suggest that GC genes of DNA methylation may lead to the erosion of cartilage in KBD, which may help us in understanding the epigenetic alteration of KBD.

| S-EPMC8808895 | biostudies-literature

Comparison of microRNA expression profiles of Kashin-Beck disease, osteoarthritis and rheumatoid arthritis.

Project description:Kashin-Beck disease (KBD) is a chronic osteochondropathy with unclear pathogeny. In this study, we compared the microRNA expression profiles of 16 KBD patients, 16 osteoarthritis (OA) patients and 16 rheumatoid arthritis (RA) patients and 16 healthy controls in their blood specimens. miRNAs expression profiling was performed using Exiqon miRCURY LNATM miRNAs Array. miRNAs target genes were predicted using miRror suite. Another independent mRNA expression profile dataset of 20 KBD patients and 15 healthy controls were integrated with the miRNA expression profiles of KBD. We identified 140 differently expressed miRNAs in KBD vs.ControlsGO enrichment analysis found that hypoxia, Wnt receptor signaling pathway and vitamin B6 biosynthesis related GO terms were significantly overrepresented in the target genes of differently expressed miRNAs in KBD vs.Control18 differently expressed common miRNAs were identified in KBD vs. Control, KBD vs. OA and KBD vs. RA. Integrating the lists of differently expressed miRNA target genes and mRNA differently expressed genes detected 6 common genes for KBD. Our results demonstrated the altered miRNAs expression profiles of KBD comparing to healthy controls, OA and RA, which provide novel clues for clarifying the mechanism of KBD.

| S-EPMC5428653 | biostudies-literature

Pathway-based network analyses and candidate genes associated with Kashin-Beck disease.

Project description:To perform a comprehensive analysis focusing on the biological functions and interactions of Kashin-Beck disease (KBD)-related genes to provide information towards understanding the pathogenesis of KBD.A retrospective, integrated bioinformatics analysis was designed and conducted. First, by reviewing the literature deposited in PubMed, we identified 922 genes genetically associated with KBD. Then, biological function and network analyses were conducted with Cytoscape software. Moreover, KBD specific molecular network analysis was conducted by Cytocluster using the Molecular Complex Detection Algorithm (MCODE).The biological function enrichment analysis suggested that collagen catabolic process, protein activation cascade, cellular response to growth factor stimulus, skeletal system development, and extrinsic apoptosis played important roles in KBD development. The apoptosis pathway, NF-kappa B signaling pathway, and the glutathione metabolism pathway were significantly enriched in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway network, suggesting that these pathways may play key roles in KBD occurrence and development. MCODE clusters showed that in top 3 clusters, 54 of KBD-related genes were included in the network and 110 candidate genes were discovered might be potentially related to KBD.The 110 candidate genes discovered in the current study may be related to the development of KBD. The expression changes of apoptosis and oxidative stress-related genes might serve as biomarkers for early diagnosis and treatment of KBD.

| S-EPMC6504273 | biostudies-literature

WISP1 Is Involved in the Pathogenesis of Kashin-Beck Disease via the Autophagy Pathway.

Project description:ObjectiveKashin-Beck disease (KBD) is a kind of endemic and chronic osteochondropathy in China. This study aims to explore the functional relevance and potential mechanism of Wnt-inducible signaling pathway protein 1 (WISP1) in the pathogenesis of KBD.DesignKBD and control cartilage specimens were collected for tissue section observation and primary chondrocyte culture. Firstly, the morphological and histopathological observations were made under a light and electron microscope. Then, the expression levels of WISP1 as well as molecular markers related to the autophagy pathway and extracellular matrix (ECM) synthesis were detected in KBD and control chondrocytes by qRT-PCR, Western blot, and immunohistochemistry. Furthermore, the lentiviral transfection technique was applied to make a WISP1 knockdown cell model based on KBD chondrocytes. In vitro intervention experiments were conducted on the C28/I2 human chondrocyte cell line using human recombinant WISP1 (rWISP1).ResultsThe results showed that the autolysosome appeared in the KBD chondrocytes. The expression of WISP1 was significantly higher in KBD chondrocytes. Additionally, T-2 toxin, a risk factor for KBD onset, could up-regulate the expression of WISP1 in C28/I2. The autophagy markers ATG4C and LC3II were upregulated after the low-concentration treatment of T-2 toxin and downregulated after the high-concentration treatment. After knocking down WISP1 expression in KBD chondrocytes, MAP1LC3B decreased while ATG4C and COL2A1 increased. Moreover, the rWISP1 protein treatment in C28/I2 chondrocytes could upregulate the expression of ATG4C and LC3II at the beginning and downregulate them then.ConclusionsOur study suggested that WISP1 might play a role in the pathogenesis of KBD through autophagy.

| S-EPMC10671535 | biostudies-literature

Prevalence of hand osteoarthritis and knee osteoarthritis in Kashin-Beck disease endemic areas and non Kashin-Beck disease endemic areas: A status survey.

Project description:Osteoarthritis (OA) is a considerable health problem worldwide, and the prevalence of OA varies in different regions. In this study, the prevalence of OA in Kashin-Beck disease (KBD) and non-KBD endemic areas was examined, respectively. According to monitoring data, 4 types of regions (including none, mild, moderate and high KBD endemic areas) in Heilongjiang and Jilin provinces were selected. All local residents were eligible for inclusion criteria have undergone X-ray images of hands and anteroposterior image of knees. A total of 1673 cases were collected, 1446 cases were analyzed after removing the KBD patients (227). The overall hand OA and knee OA detection rates were 33.3% (481/1446) and 56.6% (818/1446), respectively. After being standardized by age, the detection rate of hand OA in the KBD endemic areas was significantly higher than that in the non-endemic endemic areas. Differently, there was no significant difference in the detection rates of knee OA between the KBD endemic areas and the non-endemic area. The correlation coefficient between the severity of OA and the severity of knee OA was 0.358 and 0.197 in the KBD and non-KBD endemic areas, respectively. Where the KBD historical prevalence level was higher, the severity of the residents' hand OA was more serious. The detection rates of hand OA and knee OA increased with age. The detection rate of knee OA increased with the increase in body mass index. The prevalence of hand OA was closely related to the pathogenic factors of Kashin-Beck disease, and the prevalence of knee OA had no significant correlation with KBD pathogenic factors.

| S-EPMC5761882 | biostudies-literature

Genome-wide Gene Expression profiles of Kashin-Beck Disease

Project description:We compared genome-wide gene expression profiles of articular cartilage derived from 4 KBD patients and 4 normal controls. Total RNA was isolated from cartilage samples following by being amplified, labeled and hybridized to Agilent human 1A 22k microarray chip(G4110B).

2011-10-01 | E-MEXP-3196 | biostudies-arrayexpress

Alterations in the gut microbiota and metabolite profiles of patients with Kashin-Beck disease, an endemic osteoarthritis in China.

Project description:Kashin-Beck disease (KBD) is a severe osteochondral disorder that may be driven by the interaction between genetic and environmental factors. We aimed to improve our understanding of the gut microbiota structure in KBD patients of different grades and the relationship between the gut microbiota and serum metabolites. Fecal and serum samples collected from KBD patients and normal controls (NCs) were used to characterize the gut microbiota using 16S rDNA gene and metabolomic sequencing via liquid chromatography-mass spectrometry (LC/MS). To identify whether gut microbial changes at the species level are associated with the genes or functions of the gut bacteria in the KBD patients, metagenomic sequencing of fecal samples from grade I KBD, grade II KBD and NC subjects was performed. The KBD group was characterized by elevated levels of Fusobacteria and Bacteroidetes. A total of 56 genera were identified to be significantly differentially abundant between the two groups. The genera Alloprevotella, Robinsoniella, Megamonas, and Escherichia_Shigella were more abundant in the KBD group. Consistent with the 16S rDNA analysis at the genus level, most of the differentially abundant species in KBD subjects belonged to the genus Prevotella according to metagenomic sequencing. Serum metabolomic analysis identified some differentially abundant metabolites among the grade I and II KBD and NC groups that were involved in lipid metabolism metabolic networks, such as that for unsaturated fatty acids and glycerophospholipids. Furthermore, we found that these differences in metabolite levels were associated with altered abundances of specific species. Our study provides a comprehensive landscape of the gut microbiota and metabolites in KBD patients and provides substantial evidence of a novel interplay between the gut microbiome and metabolome in KBD pathogenesis.

| S-EPMC8553765 | biostudies-literature

Identifying discriminative features for diagnosis of Kashin-Beck disease among adolescents.

Project description:IntroductionDiagnosing Kashin-Beck disease (KBD) involves damages to multiple joints and carries variable clinical symptoms, posing great challenge to the diagnosis of KBD for clinical practitioners. However, it is still unclear which clinical features of KBD are more informative for the diagnosis of Kashin-Beck disease among adolescent.MethodsWe first manually extracted 26 possible features including clinical manifestations, and pathological changes of X-ray images from 400 KBD and 400 non-KBD adolescents. With such features, we performed four classification methods, i.e., random forest algorithms (RFA), artificial neural networks (ANNs), support vector machines (SVMs) and linear regression (LR) with four feature selection methods, i.e., RFA, minimum redundancy maximum relevance (mRMR), support vector machine recursive feature elimination (SVM-RFE) and Relief. The performance of diagnosis of KBD with respect to different classification models were evaluated by sensitivity, specificity, accuracy, and the area under the receiver operating characteristic (ROC) curve (AUC).ResultsOur results demonstrated that the 10 out of 26 discriminative features were displayed more powerful performance, regardless of the chosen of classification models and feature selection methods. These ten discriminative features were distal end of phalanges alterations, metaphysis alterations and carpals alterations and clinical manifestations of ankle joint movement limitation, enlarged finger joints, flexion of the distal part of fingers, elbow joint movement limitation, squatting limitation, deformed finger joints, wrist joint movement limitation.ConclusionsThe selected ten discriminative features could provide a fast, effective diagnostic standard for KBD adolescents.

| S-EPMC8449456 | biostudies-literature

Peripheral blood mononuclear cells, control vs. Kashin-Beck Disease

Project description:Objective: To investigate the differences between the gene expression profiles in peripheral blood mononuclear cells (PBMC) from normal controls and patients with Kashin-Beck disease (KBD). Methods: Twenty KBD patients and 12 normal subjects were selected from a KBD-endemic area and divided into four pairs of KBD vs. control (KBD, n=5 per pair; control, n=3 per pair). RNAs were respectively isolated from KBD PBMCs and normal PBMCs. Gene expression profiles were analyzed by oligonucleotide microarray.

2011-09-23 | GSE32127 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data