Irx1 mechanisms for oral epithelial basal stem cell plasticity during reepithelialization after injury.

The oral mucosa undergoes daily insults, and stem cells in the epithelial basal cell layer regenerate gingiva tissue to maintain oral health. The Iroquois Homeobox 1 (IRX1) protein is expressed in the stem cell niches in human/mouse oral epithelium and mesenchyme under homeostasis. We found that Irx1+/- heterozygous (Het) mice have delayed wound closure, delayed morphological changes of regenerated epithelium, and defective keratinocyte proliferation and differentiation during wound healing.

Transcriptional programs of Pitx2 and Tfap2a/Tfap2b controlling lineage specification of mandibular epithelium during tooth initiation.

How the dorsal-ventral axis of the vertebrate jaw, particularly the position of tooth initiation site, is established remains a critical and unresolved question. Tooth development starts with the formation of the dental lamina, a localized thickened strip within the maxillary and mandibular epithelium. To identify transcriptional regulatory networks (TRN) controlling the specification of dental lamina from the naïve mandibular epithelium, we utilized Laser Microdissection coupled low-input RNA-seq (LMD-RNA-seq) to profile gene expression of different domains of the mandibular epithelium along the dorsal-ventral axis.

RNA Technology to Regenerate and Repair Alveolar Bone Defects.

() targets multiple signaling pathways that are involved in osteogenic differentiation and bone development. However, its therapeutic function in osteogenesis and bone regeneration remains unknown. In this study, we use in vitro and in vivo models to investigate the molecular function of overexpression and inhibition using a plasmid-based miR inhibitor system (PMIS) on osteogenic differentiation and bone regeneration.

Epigenetic Regulation of Ameloblast Differentiation by HMGN Proteins.

Dental enamel formation is coordinated by ameloblast differentiation, production of enamel matrix proteins, and crystal growth. The factors regulating ameloblast differentiation are not fully understood. Here we show that the high mobility group N (HMGN) nucleosomal binding proteins modulate the rate of ameloblast differentiation and enamel formation.

Wolf-Hirschhorn syndrome candidate 1 (Whsc1) methyltransferase signals via a Pitx2-miR-23/24 axis to effect tooth development.

Wolf-Hirschhorn syndrome (WHS) is a developmental disorder attributed to a partial deletion on the short arm of chromosome 4. WHS patients suffer from oral manifestations including cleft lip and palate, hypodontia, and taurodontism. WHS candidate 1 (WHSC1) gene is a H3K36-specific methyltransferase that is deleted in every reported case of WHS.

Exploring microRNAs in craniofacial regenerative medicine.

microRNAs (miRs) have been reported over the decades as important regulators in bone development and bone regeneration. They play important roles in maintaining the stem cell signature as well as regulating stem cell fate decisions. Thus, delivering miRs and miR inhibitors to the defect site is a potential treatment towards craniofacial bone defects.

Transcriptome analyses of murine right and left maxilla-mandibular complex.

Objective: The objective of the study was to investigate differential gene expression between murine right and left maxilla-mandibular (MxMn) complexes.

Setting And Sample Population: Wild-type (WT) C57BL/6 embryonic (E) day 14.5 (n = 3) and 18.

Genetic Variants in Protein Tyrosine Phosphatase Non-Receptor Type 23 Are Responsible for Mesiodens Formation.

A mesiodens is a supernumerary tooth located in the midline of the premaxilla. To investigate the genetic cause of mesiodens, clinical and radiographic examination were performed on 23 family members of a two-generation Hmong family. Whole exome sequencing (WES) or Sanger sequencing were performed in 22 family members and two unrelated Thai patients with mesiodens.

CACNA1S mutation-associated dental anomalies: A calcium channelopathy.

Objectives: To identify the molecular etiology of distinct dental anomalies found in eight Thai patients and explore the mutational effects on cellular functions.

Materials And Methods: Clinical and radiographic examinations were performed for eight patients. Whole exome sequencing, mutant protein modelling, qPCR, western blot analysis, scratch assays, immunofluorescence, confocal analysis, in situ hybridization, and scanning electron micrography of teeth were done.

Genetic heterogeneity and enrichment of variants in DNA-repair genes in ameloblastoma.

Objective: Ameloblastomas are a group of relatively common odontogenic tumors that frequently originate from the dental epithelium. These tumors are aggressive in nature and present as slow-growing painless cortical expansion of the jaw. Histologically, the follicular and plexiform subtypes constitute two-thirds of solid/multicystic ameloblastomas.

Exploring craniofacial and dental development with microRNAs.

microRNAs (miRs) are small RNA molecules that regulate many cellular and developmental processes. They control gene expression pathways during specific developmental time points and are required for tissue homeostasis and stem cell maintenance. miRs as therapeutic reagents in tissue regeneration and repair hold great promise and new technologies are currently being designed to facilitate their expression or inhibition.

Plasmid encoding delivered by CaCO-based nanoparticles enhances rat alveolar bone formation.

miRNAs have been shown to improve the restoration of craniofacial bone defects. This work aimed to enhance transfection efficiency and -induced bone formation in alveolar bone defects via plasmid DNA encoding delivery from CaCO nanoparticles. The CaCO/ delivery system was evaluated (microscopy, transfection efficiency, biocompatibility) and -induced alveolar bone formation was assessed via micro-computed tomography and histology.

Extracellular vesicle expansion of PMIS-miR-210 expression inhibits colorectal tumour growth via apoptosis and an XIST/NME1 regulatory mechanism.

Background: Colorectal cancer (CRC) has a high mortality rate, and therapeutic approaches to treat these cancers are varied and depend on the metabolic state of the tumour. Profiles of CRC tumours have identified several biomarkers, including microRNAs. microRNA-210 (miR-210) levels are directly correlated with CRC survival.

HMGN2 represses gene transcription via interaction with transcription factors Lef-1 and Pitx2 during amelogenesis.

The chromatin-associated high mobility group protein N2 (HMGN2) cofactor regulates transcription factor activity through both chromatin and protein interactions. Hmgn2 expression is known to be developmentally regulated, but the post-transcriptional mechanisms that regulate Hmgn2 expression and its precise roles in tooth development remain unclear. Here, we demonstrate that HMGN2 inhibits the activity of multiple transcription factors as a general mechanism to regulate early development.

MicroRNA Expression in Clear Cell Renal Cell Carcinoma Cell Lines and Tumor Biopsies: Potential Therapeutic Targets.

This study was carried out to quantitate the expression levels of microRNA-17, -19a, -34a, -155, and -210 (miRs) expressed in nine clear cell renal cell carcinoma (ccRCC) and one chromophobe renal cell carcinoma cell line with and without sarcomatoid differentiation, and in six primary kidney tumors with matching normal kidney tissues. The data in the five non-sarcomatoid ccRCC cell lines-RC2, CAKI-1, 786-0, RCC4, and RCC4/VHL-and in the four ccRCC with sarcomatoid differentiation-RCJ41T1, RCJ41T2, RCJ41M, and UOK-127-indicated that miR-17 and -19a were expressed at lower levels relative to miR-34a, -155, and -210. Compared with RPTEC normal epithelial cells, miR-34a, miR-155, and miR-210 were expressed at higher levels, independent of the sarcomatoid differentiation status and hypoxia-inducible factors 1α and 2α (HIFs) isoform expression.

acts as a tumor suppressor by negatively regulating the cluster.

Anaplastic thyroid cancer (ATC) is an aggressive, highly metastatic cancer that expresses high levels of the microRNA ( cluster. We employ an miR inhibitor system to study the function of the different miRs within the cluster based on seed sequence homology in the ATC SW579 cell line. While three of the four families were oncogenic, we uncovered a novel role for as a tumor suppressor and .

Rat Calvarial Bone Regeneration by 3D-Printed β-Tricalcium Phosphate Incorporating MicroRNA-200c.

Advanced fabrication methods for bone grafts designed to match defect sites that combine biodegradable, osteoconductive materials with potent, osteoinductive biologics would significantly impact the clinical treatment of large bone defects. In this study, we engineered synthetic bone grafts using a hybrid approach that combined three-dimensional (3D-)printed biodegradable, osteoconductive β-tricalcium phosphate (β-TCP) with osteoinductive microRNA(miR)-200c. 3D-printed β-TCP scaffolds were fabricated utilizing a suspension-enclosing projection-stereolithography (SEPS) process to produce constructs with reproducible microarchitectures that enhanced the osteoconductive properties of β-TCP.

Plasmid encoding microRNA-200c ameliorates periodontitis and systemic inflammation in obese mice.

The present study was conducted to characterize microRNA-200c (miR-200c) and its regulators in adipogenic differentiation, obesity, and periodontitis in obese subjects (PiOSs), and to determine the therapeutic efficacy of plasmid DNA encoding miR-200c as a treatment for PiOSs. We report that highly expressed miR-200c in gingival tissues was downregulated in diet-induced obese (DIO) mice and during adipogenic differentiation of human bone marrow mesenchymal stromal cells (hBMSCs). Local injection of lipopolysaccharide (Pg-LPS) in the maxilla interdental gingiva of DIO mice reduced miR-200c in gingival and adipose tissues and induced periodontal inflammation associated with systemic elevation of interleukin-6 (IL-6) and impaired glucose tolerance.

The miR-200 family is required for ectodermal organ development through the regulation of the epithelial stem cell niche.

The murine lower incisor ectodermal organ contains a single epithelial stem cell (SC) niche that provides epithelial progenitor cells to the continuously growing rodent incisor. The dental stem cell niche gives rise to several cell types and we demonstrate that the miR-200 family regulates these cell fates. The miR-200 family is highly enriched in the differentiated dental epithelium and absent in the stem cell niche.

Gene-environment interaction in molar-incisor hypomineralization.

Molar incisor hypomineralization (MIH) is an enamel condition characterized by lesions ranging in color from white to brown which present rapid caries progression, and mainly affects permanent first molars and incisors. These enamel defects usually occur when there are disturbances during the mineralization or maturation stage of amelogenesis. Both genetic and environmental factors have been suggested to play roles in MIH's development, but no conclusive risk factors have shown the source of the disease.

MicroRNA function in craniofacial bone formation, regeneration and repair.

Bone formation in the craniofacial complex is regulated by cranial neural crest (CNC) and mesoderm-derived cells. Different elements of the developing skull, face, mandible, maxilla (jaws) and nasal bones are regulated by an array of transcription factors, signaling molecules and microRNAs (miRs). miRs are molecular modulators of these factors and act to restrict their expression in a temporal-spatial mechanism.

Ectodermal Organ Development Is Regulated by a Signaling Axis.

The developmental role of in ectodermal organs has been characterized using murine knockout models. We generated a conditional over-expression (COEL) mouse to determine the role of expression in epithelial structures at later stages of development after endogenous expression switches to the mesenchyme. over expression (OE) in the oral epithelium creates a new dental epithelial stem cell niche that significantly increases incisor growth.

Controls Periderm and Rugae Development to Inhibit Oral Adhesions.

In humans, ankyloglossia and cleft palate are common congenital craniofacial anomalies, and these are regulated by a complex gene regulatory network. Understanding the genetic underpinnings of ankyloglossia and cleft palate will be an important step toward rational treatment of these complex anomalies. We inactivated the Sry (sex-determining region Y)-box 2 () gene in the developing oral epithelium, including the periderm, a transient structure that prevents abnormal oral adhesions during development.

interactions specify progenitor oral/dental epithelial cell signaling centers.

Epithelial signaling centers control epithelial invagination and organ development, but how these centers are specified remains unclear. We report that (the first transcriptional marker for tooth development) controls the embryonic formation and patterning of epithelial signaling centers during incisor development. We demonstrate using / ( ) and mice that loss of delays epithelial invagination, and decreases progenitor cell proliferation and dental epithelium cell differentiation.