Unknown,Transcriptomics,Genomics,Proteomics

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Expression status of mRNA for sex hormone receptors in human dental pulp cells and the response to sex hormones in the cells

ABSTRACT: Objectives: Sex hormone receptors are reported to be present in human dental pulp (HDP) cells. The purpose of this study was to examine the biological significance of estrogen and androgen receptors (ER and AR, respectively) in HDP cells. Design: We isolated HDP cells expressing ER- and AR-mRNAs and investigated the expression status of the receptors and the response to sex hormones in the cells. Results: HDP cells expressing ER- and/or AR-mRNAs had the ability to form alizarin red S-positive nodules in which calcium and phosphorus were deposited in vitro and to differentiate into odontoblasts-like cells and dentin-like tissue in vivo. Individual clones isolated from HDP cells exhibited a different expression pattern of mRNA for ER and AR. Some clones expressed ERM-NM-1- and/or ERM-NM-2-mRNAs and the others coexpressed ER- and AR-mRNAs. Using the Ingenuity software, we found that 17M-NM-2-estradiol (E2) and dihydrotestosterone (DHT) could act directly on HDP cells through ER- or androgen signaling-mediated mechanisms. E2 or DHT stimulated the mRNA expression for genes related to odontogenesis of dentin-containing teeth and odontoblast differentiation, suggesting that ER and AR in HDP cells may be involved in dentinogenesis. Conclusions: Our findings provide new insights into the biological significance of sex hormone receptors in HDP cells. Gene expression profiles of human dental pulp cells derived from one male patient were compared between cells treated with 10^-6 M 5alpha-dihydrotestosterone and cells treated with vehicle. Each sample has one replicate. Gene expression profiles of human dental pulp cells derived from one female patient were compared between cells treated with 10^-9 M 17beta-estradiol and cells treated with vehicle. Each sample has one replicate.

ORGANISM(S): Homo sapiens

SUBMITTER: Tomoko Kobayashi

PROVIDER: E-GEOD-44677 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Enforced enhancement of H3K4me3 and H3K27ac, active chromatin marks, by inhibiting histone demethylases and deacetylases is positively linked with hard tissue formation by inducing matrix synthesis and osteo/odontogenic differentiation. However, the key endogenous epigenetic modifier of odontoblasts to regulate the expression of the genes coding dentin extracellular matrix (ECM) proteins has not been identified yet. We herein focused on IκBζ, which was originally identified as transcriptional regulator for NF-B and recently regarded as the local epigenetic modifier by independently on NF-B, and demonstrated that the IκBζ null mice exhibited thicker dentin width and narrower pulp chamber with aged mice having more drastic phenotypes. At 6 months old, dentin fluorescent labeling exhibited that dentin synthesis was significantly accelerated in the incisors of IκBζ null mice. In molars of IκBζ null mice, aggressive reactionary dentin adjacent to pulp horn was exhibited. Mechanistically, COL1A2 and COL1A1 collagen genes were increased in the odontoblasts rich fraction of IκBζ null mice than that of wild type in vivo and human odontoblasts-like cells transfected with siRNA for IκBζ than the control siRNA transfected cells in vitro. Further, the direct binding of IκBζ to COL1A2 promoter suppressed COL1A2 expression and the local active chromatin status marked with H3K4me3. By whole-genomic identification of H3K4me3 enrichments revealed that ECM and ECM organization-related gene loci were selectively activated by the knockdown of IκBζ, which consistently resulted in the up-regulation of these genes. Collectively, these results indicated that IκBζ is the key negative regulator of dentin formation in odontoblasts since the deletion of IκBζ expression enhanced dentin formation by inducing dentin ECM and ECM organization-related gene expression via altering the local chromatin status marked by H3K4me3. Therefore, IκBζ is a potential target for improving the clinical outcomes of dentin regeneration therapies such as pulp capping and pulp revitalization procedures.

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Expression status of mRNA for sex hormone receptors in human dental pulp cells and the response to sex hormones in the cells

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