scholarly journals Comprehensive analysis of pathological changes in hip joint capsule of patients with developmental dysplasia of the hip

2021 ◽  
Vol 10 (9) ◽  
pp. 558-570
Author(s):  
Chuan Li ◽  
Zhi Peng ◽  
You Zhou ◽  
Yongyue Su ◽  
Pengfei Bu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Differentially Expressed Genes ◽  
Hip Joint ◽  
Cyclin B1 ◽  
Developmental Dysplasia ◽  
Joint Capsule ◽  
Differentially Expressed ◽  
Healthy Controls ◽  
Collagen Fibres ◽  
Dysplasia Of The Hip

Aims Developmental dysplasia of the hip (DDH) is a complex musculoskeletal disease that occurs mostly in children. This study aimed to investigate the molecular changes in the hip joint capsule of patients with DDH. Methods High-throughput sequencing was used to identify genes that were differentially expressed in hip joint capsules between healthy controls and DDH patients. Biological assays including cell cycle, viability, apoptosis, immunofluorescence, reverse transcription polymerase chain reaction (RT-PCR), and western blotting were performed to determine the roles of the differentially expressed genes in DDH pathology. Results More than 1,000 genes were differentially expressed in hip joint capsules between healthy controls and DDH. Both gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that extracellular matrix (ECM) modifications, muscle system processes, and cell proliferation were markedly influenced by the differentially expressed genes. Expression of Collagen Type I Alpha 1 Chain (COL1A1), COL3A1, matrix metalloproteinase-1 (MMP1), MMP3, MMP9, and MMP13 was downregulated in DDH, with the loss of collagen fibres in the joint capsule. Expression of transforming growth factor beta 1 (TGF-β1) was downregulated, while that of TGF-β2, Mothers against decapentaplegic homolog 3 (SMAD3), and WNT11 were upregulated in DDH, and alpha smooth muscle actin (αSMA), a key myofibroblast marker, showed marginal increase. In vitro studies showed that fibroblast proliferation was suppressed in DDH, which was associated with cell cycle arrest in G0/G1 and G2/M phases. Cell cycle regulators including Cyclin B1 (CCNB1), Cyclin E2 (CCNE2), Cyclin A2 (CCNA2), Cyclin-dependent kinase 1 (CDK1), E2F1, cell division cycle 6 (CDC6), and CDC7 were downregulated in DDH. Conclusion DDH is associated with the loss of collagen fibres and fibroblasts, which may cause loose joint capsule formation. However, the degree of differentiation of fibroblasts to myofibroblasts needs further study. Cite this article: Bone Joint Res 2021;10(9):558–570.

scholarly journals METTL3-mediated M6a Modification Regulates Cell Cycle Progression of Dental Pulp Stem Cells

2021 ◽  
Author(s):  
Haiyun Luo ◽  
Wenjing Liu ◽  
Yanli Zhang ◽  
Xiao Jiang ◽  
Shiqing Wu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Tissue Engineering ◽  
Stem Cells ◽  
Flow Cytometry ◽  
Differentially Expressed Genes ◽  
Dental Pulp ◽  
Cell Cycle Control ◽  
Dental Pulp Stem Cells ◽  
Differentially Expressed ◽  
Expression Level

Abstract Background: Dental pulp stem cells (DPSCs) exhibited self-renewal, pluripotency capacity and served as promising cells source in endodontic regeneration and tissue engineering. Meanwhile, the regenerative capacity of DPSCs is limited and reduced in long lifespan. N6-methyladenosine (m6A) is the most prevalent, reversible internal modification in RNAs. The methyltransferases complex and demethylases mediated m6A methylation and cooperated to impact various biological processes associated with stem cell fate determination. However, the biological effect of m6A methylation in DPSCs remained unclear. Methods: Cell surface markers and differentiation potential of primary DPSCs were identified and m6A immunoprecipitation with deep sequencing (m6A RIP-seq) was used to uncover characteristics of m6A modifications in DPSCs transcriptome. Expression level of m6A-related genes were evaluated in immature/mature pulp tissues and cells. Lentiviral vectors were constructed to knockdown or overexpress methyltransferase like 3 (METTL3). Cell morphology, viability, senescence and apoptosis were further analyzed by β-galactosidase, TUNEL staining and flow cytometry. Bioinformatic analysis combing m6A RIP and shMETTL3 RNA-seq was used to functionally enrich overlapped genes and screen target of METTL3. Cell cycle distributions were assayed by flow cytometry and m6A RIP-qPCR was used to confirm METTL3 mediated m6A methylation in DPSCs. Results: Here, m6A peaks distribution, binding area and motif in DPSCs were first revealed by m6A RIP-seq. We also found a relative high expression level of METTL3 in immature DPSCs with superior regenerative potential and METTL3 knockdown induced cell apoptosis and senescence. Furthermore, Conjoint analysis of m6A RIP and RNA-sequencing showed differentially expressed genes affected by METTL3 depletion was mainly enriched in cell cycle, mitosis and alteration of METTL3 expression resulted in cell cycle arrest which indicated METTL3 make essential effect in cell cycle control. To further investigate underlying mechanisms, we explored proteins interaction network of differentially expressed genes and Polo-like Kinase 1 (PLK1), a critical cycle modulator was identified as target of METTL3-mediated m6A methylation in DPSCs. Conclusions: These results revealed m6A methylated hallmarks in DPSCs and a regulatory role of METTL3 in cell cycle control. Our study shed light on therapeutic approaches in vital pulp therapy and serve new insight in stem cells based tissue engineering.

scholarly journals Association of differentially expressed genes and autoantibody type in patients with systemic sclerosis

Rheumatology ◽  
2020 ◽  
Author(s):  
Jun Inamo
Keyword(s):  
Gene Expression ◽  
Differentially Expressed Genes ◽  
Cellular Response ◽  
Rna Polymerase Iii ◽  
Skin Lesions ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Study Cohort ◽  
Healthy Controls ◽  
Specific Autoantibody

Abstract Objectives The aims of this study were to investigate the relationship between the type of autoantibody and gene expression profile in skin lesions from patients with SSc, and to identify specific dysregulated pathways in SSc patients compared with healthy controls. Methods Sixty-one patients with SSc from the Genetics vs Environment in Scleroderma Outcome Study cohort and 36 healthy controls were included in this study. Differentially expressed genes were extracted and functional enrichment and pathway analysis were conducted. Results Compared with healthy controls, lists containing 2, 71, 10, 144 and 78 differentially expressed genes were created for patients without specific autoantibody, ACA, anti-U1 RNP antibody (RNP), anti-RNA polymerase III antibody (RNAP) and anti-topoisomerase I antibody (ATA), respectively. While part of the enriched pathways overlapped, distinct pathways were identified except in those patients lacking specific autoantibody. The distinct enriched pathways included ‘keratinocyte differentiation’ for ACA, ‘nuclear factor κB signalling’ and ‘cellular response to TGF-β stimulus’ for RNAP, ‘interferon α/β signalling’ for RNP, and ‘cellular response to stress’ for ATA. Cell type signature score analysis revealed that macrophages/monocytes, endothelial cells and fibroblasts were associated with ACA, RNAP, ATA and the severity of the SSc skin lesions. Conclusion Pathogenic pathways were identified according to the type of autoantibody by leveraging gene expression data of patients and controls from a multicentre cohort. The current study may promote the search for new therapeutic targets for SSc.

scholarly journals Transcriptional modulator ZBED6 affects cell cycle and growth of human colorectal cancer cells

2015 ◽  
Vol 112 (25) ◽  
pp. 7743-7748 ◽  
Author(s):  
Muhammad Akhtar Ali ◽  
Shady Younis ◽  
Ola Wallerman ◽  
Rajesh Gupta ◽  
Leif Andersson ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Lines ◽  
Differentially Expressed Genes ◽  
Target Genes ◽  
Egf Receptor ◽  
Differentially Expressed ◽  
Striking Difference ◽  
Human Colorectal Cancer ◽  
Chip Sequencing

The transcription factor ZBED6 (zinc finger, BED-type containing 6) is a repressor of IGF2 whose action impacts development, cell proliferation, and growth in placental mammals. In human colorectal cancers, IGF2 overexpression is mutually exclusive with somatic mutations in PI3K signaling components, providing genetic evidence for a role in the PI3K pathway. To understand the role of ZBED6 in tumorigenesis, we engineered and validated somatic cell ZBED6 knock-outs in the human colorectal cancer cell lines RKO and HCT116. Ablation of ZBED6 affected the cell cycle and led to increased growth rate in RKO cells but reduced growth in HCT116 cells. This striking difference was reflected in the transcriptome analyses, which revealed enrichment of cell-cycle–related processes among differentially expressed genes in both cell lines, but the direction of change often differed between the cell lines. ChIP sequencing analyses displayed enrichment of ZBED6 binding at genes up-regulated in ZBED6-knockout clones, consistent with the view that ZBED6 modulates gene expression primarily by repressing transcription. Ten differentially expressed genes were identified as putative direct gene targets, and their down-regulation by ZBED6 was validated experimentally. Eight of these genes were linked to the Wnt, Hippo, TGF-β, EGF receptor, or PI3K pathways, all involved in colorectal cancer development. The results of this study show that the effect of ZBED6 on tumor development depends on the genetic background and the transcriptional state of its target genes.

scholarly journals PO-046 Gene expression profiling of peripheral blood mononuclear cells in young male trampoline athletes

2018 ◽  
Vol 1 (3) ◽  
Author(s):  
Li Gao ◽  
Yong Jie Yang ◽  
En Qi Li ◽  
Jia Ning Mao
Keyword(s):  
Gene Expression ◽  
Differentially Expressed Genes ◽  
Bone Health ◽  
Expression Profiling ◽  
Molecular Mechanisms ◽  
Interaction Network ◽  
Differentially Expressed ◽  
Signal Pathways ◽  
Healthy Controls ◽  
Mineral Density

Objective Evidence indicates that physical activity influence bone health. However, the molecular mechanisms mediating the beneficial adaptations to exercise are not well understood. The purpose of this study was to examine the differentially expressed genes in PBMC between athletes and healthy controls, and to analyze the important functional genes and signal pathways that cause increased bone mineral density in athletes, in order to further reveal the molecular mechanisms of exercise promoting bone health. Methods Five professional trampoline athletes and five age-matched untrained college students participated in this study. Used the human expression Microarray V4.0 expression profiling chip to detect differentially expressed genes in the two groups, and performed KEGG Pathway analysis and application of STRING database to construct protein interaction Network; Real-Time PCR technology was used to verify the expression of some differential genes.  Results Compared with healthy controls, there were significant improvement in lumbar spine bone mineral density, and 236 up-regulated as well as 265 down-regulated in serum samples of athletes. The differentially expressed genes involved 28 signal pathways, such as cell adhesion molecules. Protein interaction network showed that MYC was at the core node position. Real-time PCR results showed that the expression levels of CD40 and ITGα6 genes in the athletes were up-regulated compared with the healthy controls, the detection results were consistent with that of the gene chip. Conclusions The findings highlight that long-term high-intensity trampoline training could induce transcriptional changes in PBMC of the athletes. These data suggest that gene expression fingerprints can serve as a powerful research tool to design novel strategies for monitoring exercise. The findings of the study also provide support for the notion that PBMC could be used as a substitute to study exercise training that affects bone health.

scholarly journals Wfs1 and Related Molecules as Key Candidate Genes in the Hippocampus of Depression

2021 ◽  
Vol 11 ◽  
Author(s):  
Jing Yang ◽  
Chaoqin Chen ◽  
Xiaoyuan Jin ◽  
Lu Liu ◽  
Jiajia Lin ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Mouse Model ◽  
Differentially Expressed Genes ◽  
Molecular Mechanisms ◽  
Visual Analysis ◽  
Pathological Process ◽  
Differentially Expressed ◽  
Mild Stress ◽  
Ppi Networks ◽  
Chemokine Signaling

BackgroundDepression is a prevalent mental disorder, which is difficult to diagnose and treat due to its unclear pathogenic mechanisms. The discovery of novel and effective therapeutic targets for depression is urgently needed. The hippocampus is a crucial region involved in depression and has been a therapeutic target for many antidepressants. Thus, it is beneficial for comprehensive research to be carried out on the molecular mechanisms of the hippocampus involved in the pathogenesis of depression. This study aims to investigate the differentially expressed genes (DEG) in the hippocampus in a chronic unpredictable mild stress (CUMS) mouse model.MethodThe study obtained GSE84183 from the GEO database. The R language screened the differential expression genes (DEG) in the hippocampus tissue of depressed mice, and the enrichment pathways of DEGs were analyzed. A protein-protein interaction (PPI) network was constructed in the STRING database and visualized in Cytoscape software. MicroRNAs for these DEGs were obtained from TarBase and mortar base databases, and transcription factors (TF) related to DEG were predicted from the ENCODE database. Both networks used the visual analysis platform NetworkAnalyst. Finally, the microRNA-TF network was integrated based on the above two networks and imported into Cytoscape for further analysis.ResultsThis study screened 325 differentially expressed genes, containing 42 downregulated genes and 283 upregulated genes. Most of these genes are enriched in the cell cycle and the chemokine signaling pathway. Meanwhile, Wfs1, one of the top ten DEGs, was identified as the key regulator of the cell cycle and the participator in the highest number of modules screened out in PPI networks. Wfs1-related molecules, including UBTF, mmu-mir-17-5p, and mmu-mir-7b-5p, were therefore screened out. Furthermore, we confirmed the downregulation of Wfs1 and upregulation of UBTF/mmu-mir-17-5p/mmu-mir-7b-5p in the hippocampus of the CUMS mouse model. Our data indicate that Wfs1 and related molecules were predicted to be associated with the pathological process of depression. This research provided potential new molecular targets of stress-induced depression.

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