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Omics score: 1042

Transcriptome analysis of periodontitis-associated fibroblasts by CAGE sequencing identified DLX5 and RUNX2 long variant as novel regulators involved in periodontitis

ABSTRACT: Transcriptome analysis of periodontitis-associated fibroblasts by CAGE sequencing identified DLX5 and RUNX2 long variant as novel regulators involved in periodontitis Overall design: Transcriptome analysis of periodontitis-associated fibroblasts by CAGE sequencing identified DLX5 and RUNX2 long variant as novel regulators involved in periodontitis

INSTRUMENT(S): [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array

SUBMITTER: Masafumi Horie

PROVIDER: GSE81984 | GEO | 2016-09-15

SECONDARY ACCESSION(S): GSE81870PRJNA323558 GSE81982

REPOSITORIES: GEO

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Transcriptome analysis of periodontitis-associated fibroblasts by CAGE sequencing identified DLX5 and RUNX2 long variant as novel regulators involved in periodontitis.

Horie Masafumi M Yamaguchi Yoko Y Saito Akira A Nagase Takahide T Lizio Marina M Itoh Masayoshi M Kawaji Hideya H Lassmann Timo T Carninci Piero P Forrest Alistair R R AR Hayashizaki Yoshihide Y Suzutani Tatsuo T Kappert Kai K Micke Patrick P Ohshima Mitsuhiro M

Scientific reports 20160920

Periodontitis is affecting over half of the adult population, and represents a major public health problem. Previously, we isolated a subset of gingival fibroblasts (GFs) from periodontitis patients, designated as periodontitis-associated fibroblasts (PAFs), which were highly capable of collagen degradation. To elucidate their molecular profiles, GFs isolated form healthy and periodontitis-affected gingival tissues were analyzed by CAGE-seq and integrated with the FANTOM5 atlas. GFs from healthy ...[more]

PMID: 27645561

Similar Datasets

Transcriptome analysis of periodontitis-associated fibroblasts by CAGE sequencing identified DLX5 and RUNX2 long variant as novel regulators involved in periodontitis.

Project description:Periodontitis is affecting over half of the adult population, and represents a major public health problem. Previously, we isolated a subset of gingival fibroblasts (GFs) from periodontitis patients, designated as periodontitis-associated fibroblasts (PAFs), which were highly capable of collagen degradation. To elucidate their molecular profiles, GFs isolated form healthy and periodontitis-affected gingival tissues were analyzed by CAGE-seq and integrated with the FANTOM5 atlas. GFs from healthy gingival tissues displayed distinctive patterns of CAGE profiles as compared to fibroblasts from other organ sites and characterized by specific expression of developmentally important transcription factors such as BARX1, PAX9, LHX8, and DLX5. In addition, a novel long non-coding RNA associated with LHX8 was described. Furthermore, we identified DLX5 regulating expression of the long variant of RUNX2 transcript, which was specifically active in GFs but not in their periodontitis-affected counterparts. Knockdown of these factors in GFs resulted in altered expression of extracellular matrix (ECM) components. These results indicate activation of DLX5 and RUNX2 via its distal promoter represents a unique feature of GFs, and is important for ECM regulation. Down-regulation of these transcription factors in PAFs could be associated with their property to degrade collagen, which may impact on the process of periodontitis.

| S-EPMC5028883 | BioStudies

Transcriptome analysis of periodontitis-associated fibroblasts by CAGE sequencing identified DLX5 and RUNX2 long variant as novel regulators involved in periodontitis.

Project description:Transcriptome analyses of normal gingival fibroblasts after knockdown of DLX5 and RUNX2 long forms. Overall design: Knockdown of DLX5 and RUNX2 long forms by lenti virus vector

2016-09-15 | GSE81870 | GEO

Transcriptome analysis of periodontitis-associated fibroblasts by CAGE sequencing identified DLX5 and RUNX2 long variant as novel regulators involved in periodontitis

Project description:Transcriptome analysis of periodontitis-associated fibroblasts by CAGE sequencing identified DLX5 and RUNX2 long variant as novel regulators involved in periodontitis

| PRJNA323558 | ENA

Homo sapiens

Project description:Transcriptome analysis of periodontitis-associated fibroblasts by CAGE sequencing identified DLX5 and RUNX2 long variant as novel regulators involved in periodontitis.

| PRJNA322829 | ENA

Different Methylation Patterns of RUNX2, OSX, DLX5 and BSP in Osteoblastic Differentiation of Mesenchymal Stem Cells.

Project description:OBJECTIVE:Runt-related transcription factor 2 (RUNX2) and osterix (OSX) as two specific osteoblast transcription factors and distal-less homeobox 5 (DLX5) as a non-specific one are of paramount importance in regulating osteoblast related genes including osteocalcin, bone sialoprotein (BSP), osteopontin and collagen type I?1. The present study sets out to investigate whether epigenetic regulation of these genes is important in osteoblastic differentiation of mesenchymal stem cells (MSCs). MATERIALS AND METHODS:In this experimental study, MSCs were differentiated to osteoblasts under the influence of the osteogenic differentiation medium. DNA and RNA were extracted at days 0, 7, 14 and 21 from MSCs differentiating to osteoblasts. Promoter regions of RUNX2, OSX, DLX5 and BSP were analyzed by methylation-specific PCR (MSP). Gene expression was analyzed during osteoblastic differentiation by quantitative real-time polymerase chain reaction (PCR). RESULTS:MSP analysis revealed that promoter methylation status did not change in RUNX2, DLX5 and BSP during MSC osteoblastic differentiation. In contrast, OSX promoter showed a dynamic change in methylation pattern. Moreover, RUNX2, OSX, DLX5 and BSP promoter regions showed three different methylation patterns during MSC differentiation. Gene expression analyses confirmed these results. CONCLUSION:The results show that in differentiation of MSCs to osteoblasts, epigenetic regulation of OSX may play a leading role.

| S-EPMC4393674 | BioStudies

Dlx5-augmentation in neural crest cells reveals early development and differentiation potential of mouse apical head mesenchyme.

Project description:Neural crest cells (NCCs) give rise to various tissues including neurons, pigment cells, bone and cartilage in the head. Distal-less homeobox 5 (Dlx5) is involved in both jaw patterning and differentiation of NCC-derivatives. In this study, we investigated the differentiation potential of head mesenchyme by forcing Dlx5 to be expressed in mouse NCC (NCC<sup>Dlx5</sup>). In NCC<sup>Dlx5</sup> mice, differentiation of dermis and pigment cells were enhanced with ectopic cartilage (ec) and heterotopic bone (hb) in different layers at the cranial vertex. The ec and hb were derived from the early migrating mesenchyme (EMM), the non-skeletogenic cell population located above skeletogenic supraorbital mesenchyme (SOM). The ec developed within Foxc1<sup>+</sup>-dura mater with increased PDGFR? signalling, and the hb formed with upregulation of BMP and WNT/?-catenin signallings in Dermo1<sup>+</sup>-dermal layer from E11.5. Since dermal cells express Runx2 and Msx2 in the control, osteogenic potential in dermal cells seemed to be inhibited by an anti-osteogenic function of Msx2 in normal context. We propose that, after the non-skeletogenic commitment, the EMM is divided into dermis and meninges by E11.5 in normal development. Two distinct responses of the EMM, chondrogenesis and osteogenesis, to Dlx5-augmentation in the NCC<sup>Dlx5</sup> strongly support this idea.

| S-EPMC7822927 | BioStudies

Dysbacteriosis-Derived Lipopolysaccharide Causes Embryonic Osteopenia through Retinoic-Acid-Regulated DLX5 Expression.

Project description:Growing evidence suggests an adverse impact of gut microbiota dysbiosis on human health. However, it remains unclear whether embryonic osteogenesis is affected by maternal gut dysbacteriosis. In this study, we observed that elevated lipopolysaccharide (LPS) levels led to skeletal developmental retardation in an established mouse model of gut microbiota dysbiosis. Using chick embryos exposed to dysbacteriosis-derived LPS, we found restriction in the development of long bones as demonstrated by Alcian blue and alizarin red staining. Micro-CT and histological analysis exhibited decreased trabecular volume, bone mineral density, and collagen production, as well as suppressed osteoblastic gene expression (Ocn, Runx2, Osx, and Dlx5) in chick embryonic phalanges following LPS treatment. Atomic force microscopy manifested decreased roughness of MC3T3-E1 cells and poorly developed matrix vesicles (MVs) in presence of LPS. The expression of the aforementioned osteoblastic genes was suppressed in MC3T3-E1 cells as well. High-throughput RNA sequencing indicated that retinoic acid (RA) may play an important role in LPS-induced osteopenia. The addition of RA suppressed Dlx5 expression in MC3T3-E1 cells, as was also seen when exposed to LPS. Quantitative PCR, Western blot, and immunofluorescent staining showed that retinoic acid receptor ? (RAR?) was upregulated by LPS or RA treatment, while the expression of DLX5 was downregulated. CYP1B1 expression was increased by LPS treatment in MC3T3-E1 cells, which might be attributed to the increased inflammatory factors and subsequently activated NF-?B signaling. Eventually, blocking RA signals with AGN193109 successfully restored LPS-inhibited osteoblastic gene expression. Taken together, our data reveals that maternal gut microbiota dysbiosis can interfere with bone ossification, in which Dlx5 expression regulated by RA signaling plays an important role.

| S-EPMC7177785 | BioStudies

Mendelian randomization analysis identified genes potentially pleiotropically associated with periodontitis.

Project description:<h4>Objective</h4>To prioritize genes that were pleiotropically or potentially causally associated with periodontitis.<h4>Methods</h4>We applied the summary data-based Mendelian randomization (SMR) method integrating genome-wide association study (GWAS) for periodontitis and expression quantitative trait loci (eQTL) data to identify genes that were pleiotropically associated with periodontitis. We performed separate SMR analysis using CAGE eQTL data and GTEx eQTL data. SMR analysis were done for participants of European and East Asian ancestries, separately.<h4>Results</h4>We identified multiple genes showing pleiotropic association with periodontitis in participants of European ancestry and participants of East Asian ancestry. <i>PDCD2</i> (corresponding probe: ILMN_1758915) was the top hit showing pleotropic association with periodontitis in the participants of European ancestry using CAGE eQTL data, and <i>BX093763</i> (corresponding probe: ILMN_1899903) and <i>AC104135.3</i> (corresponding probe: ENSG00000204792.2) were the top hits in the participants of East Asian ancestry using CAGE eQTL data and GTEx eQTL data, respectively.<h4>Conclusion</h4>We identified multiple genes that may be involved in the pathogenesis of periodontitis in participants of European ancestry and participants of East Asian ancestry. Our findings provided important leads to a better understanding of the mechanisms underlying periodontitis and revealed potential therapeutic targets for the effective treatment of periodontitis.

| S-EPMC8241609 | BioStudies

Dlx5 Is a cell autonomous regulator of chondrocyte hypertrophy in mice and functionally substitutes for Dlx6 during endochondral ossification.

Project description:The axial and appendicular skeleton of vertebrates develops by endochondral ossification, in which skeletogenic tissue is initially cartilaginous and the differentiation of chondrocytes via the hypertrophic pathway precedes the differentiation of osteoblasts and the deposition of a definitive bone matrix. Results from both loss-of-function and misexpression studies have implicated the related homeobox genes Dlx5 and Dlx6 as partially redundant positive regulators of chondrocyte hypertrophy. However, experimental perturbations of Dlx expression have either not been cell type specific or have been done in the context of endogenous Dlx5 expression. Thus, it has not been possible to conclude whether the effects on chondrocyte differentiation are cell autonomous or whether they are mediated by Dlx expression in adjacent tissues, notably the perichondrium. To address this question we first engineered transgenic mice in which Dlx5 expression was specifically restricted to immature and differentiating chondrocytes and not the perichondrium. Col2a1-Dlx5 transgenic embryos and neonates displayed accelerated chondrocyte hypertrophy and mineralization throughout the endochondral skeleton. Furthermore, this transgene specifically rescued defects of chondrocyte differentiation characteristic of the Dlx5/6 null phenotype. Based on these results, we conclude that the role of Dlx5 in the hypertrophic pathway is cell autonomous. We further conclude that Dlx5 and Dlx6 are functionally equivalent in the endochondral skeleton, in that the requirement for Dlx5 and Dlx6 function during chondrocyte hypertrophy can be satisfied with Dlx5 alone.

| S-EPMC2779492 | BioStudies

The Dlx5 and Dlx6 homeobox genes are essential for craniofacial, axial, and appendicular skeletal development.

Project description:Dlx homeobox genes are mammalian homologs of the Drosophila Distal-less (Dll) gene. The Dlx/Dll gene family is of ancient origin and appears to play a role in appendage development in essentially all species in which it has been identified. In Drosophila, Dll is expressed in the distal portion of the developing appendages and is critical for the development of distal structures. In addition, human Dlx5 and Dlx6 homeobox genes have been identified as possible candidate genes for the autosomal dominant form of the split-hand/split-foot malformation (SHFM), a heterogeneous limb disorder characterized by missing central digits and claw-like distal extremities. Targeted inactivation of Dlx5 and Dlx6 genes in mice results in severe craniofacial, axial, and appendicular skeletal abnormalities, leading to perinatal lethality. For the first time, Dlx/Dll gene products are shown to be critical regulators of mammalian limb development, as combined loss-of-function mutations phenocopy SHFM. Furthermore, spatiotemporal-specific transgenic overexpression of Dlx5, in the apical ectodermal ridge of Dlx5/6 null mice can fully rescue Dlx/Dll function in limb outgrowth.

| S-EPMC186247 | BioStudies

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