Msx2 Prevents Stratified Squamous Epithelium Formation in the Enamel Organ

Tooth enamel is manufactured by the inner enamel epithelium of the multilayered enamel organ. Msx2 loss-of-function mutation in a mouse model causes an abnormal accumulation of epithelial cells in the enamel organ, but the underlying mechanism by which Msx2 regulates amelogenesis is poorly understood. We therefore performed detailed histological and molecular analyses of Msx2 null mice. Msx2 null ameloblasts and stratum intermedium (SI) cells differentiated normally in the early stages of amelogenesis. However, during subsequent developmental stages, the outer enamel epithelium (OEE) became highly proliferative and transformed into a keratinized stratified squamous epithelium that ectopically expressed stratified squamous epithelium markers, including Heat shock protein 25, Loricrin, and Keratin 10. Moreover, expression of hair follicle–specific keratin genes such as Keratin 26 and Keratin 73 was upregulated in the enamel organ of Msx2 mutants. With the accumulation of keratin in the stellate reticulum (SR) region and subsequent odontogenic cyst formation, SI cells gradually lost the ability to differentiate, and the expression of Sox2 and Notch1 was downregulated, leading to ameloblast depolarization. As a consequence, the organization of the Msx2 mutant enamel organ became disturbed and enamel failed to form in the normal location. Instead, there was ectopic mineralization that likely occurred within the SR. In summary, we show that during amelogenesis, Msx2 executes a bipartite function, repressing the transformation of OEE into a keratinized stratified squamous epithelium while simultaneously promoting the development of a properly differentiated enamel organ competent for enamel formation.

Download Full-text

A contribution to the diagnosis of the small dentigerous cyst or the paradental cyst

Pesquisa Odontológica Brasileira ◽

10.1590/s1517-74912001000300010 ◽

2001 ◽

Vol 15 (3) ◽

pp. 238-246 ◽

Cited By ~ 20

Author(s):

José Humberto DAMANTE ◽

Raul Negrão FLEURY

Keyword(s):

Squamous Epithelium ◽

Statistical Significance ◽

Dentigerous Cyst ◽

Radiographic Analysis ◽

Dentigerous Cysts ◽

Enamel Epithelium ◽

Microscopic Features ◽

Stratified Squamous Epithelium ◽

Unerupted Teeth ◽

The Relationship

The aim of this study was to verify the relationship between the radiographically measured width of the pericoronal space (PS) and the microscopic features of the follicle in order to contribute to the diagnosis of small dentigerous cysts and paradental cysts. One hundred and thirty unerupted teeth (UT) and thirty-five partially erupted teeth (PET) were radiographed and extracted. The radiographic analysis consisted of measuring the width of the PS. The results of the radiographic analysis were compared with those of the histopathologic examination of the dental follicle. The width of the PS ranged from 0.1 to 5.6 mm. The most frequently observed lining of the follicles was a reduced enamel epithelium (REE) (68.4%) in UT and a hyperplastic stratified squamous epithelium (HSSE) (68.5%) in PET. Inflammation was present in 36.1% of the UT and in 82.8% of the PET. There was a statistically significant association between the presence of stratified squamous epithelium (SSE) and PS enlargement for UT (p < 0.05). There was a tendency of association between inflammation and PS enlargements in PET and, possibly, in UT, despite the absence of statistical significance. Surgically, we did not detect bone cavitation or luminal cystic contents in pericoronal spaces smaller than 5.6 mm. We suggest that the first radiographic diagnosis for a PS enlargement, in most of the routine clinical cases, should be of "inflammation of the follicle". The hypothesis of "dentigerous cyst" or "paradental cyst" is suggested as a second diagnosis. The final differential diagnosis between a small dentigerous or a paradental cyst and a pericoronal follicle depends on clinical and/or surgical findings, such as the presence of bone cavitation and cystic content.

Download Full-text

Understanding Lateral Periodontal Cyst: A Case Report

Dental Journal of Advance Studies ◽

10.1055/s-0039-1693093 ◽

2019 ◽

Vol 07 (02) ◽

pp. 099-102

Author(s):

Monica Roy Chandel ◽

Kundendu Arya Bishen ◽

Nikit Agrawal ◽

Himanshu Singh

Keyword(s):

Case Report ◽

Squamous Epithelium ◽

Maxillary Bone ◽

Pathological Correlation ◽

Enamel Epithelium ◽

Stratified Squamous Epithelium ◽

Histological Characteristics ◽

Hematoxylin And Eosin ◽

Lateral Periodontal Cyst ◽

Reduced Enamel Epithelium

AbstractLateral periodontal cysts (LPCs) are developmental in origin and are typically seen in the canine-premolar area in the mandible and less commonly in the maxilla. Reported rate of incidence of LPCs is less than 1%, and LPCs represent only 0.8% of entire central cysts of the maxillary bone. Despite its unique clinical and radiological presentation, it is finally diagnosed due to its unique histological characteristics. Here, we present one case with characteristic findings. The routine hematoxylin and eosin–stained sections revealed reduced enamel epithelium-like cystic lining that is made of thin, nonkeratinized stratified squamous epithelium along with some epithelial plaques. The clinical-radio-pathological correlation affirmed the diagnosis of LPC. The pathogenesis of LPC has been discussed.

Download Full-text

Junction of the Epithelium and Lamina Propria of the Bovine Rumen Mucosa

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100060350 ◽

1967 ◽

Vol 25 ◽

pp. 68-69

Author(s):

Al W. Stinson

Keyword(s):

Osmium Tetroxide ◽

Squamous Epithelium ◽

Short Chain Fatty Acids ◽

Chloride Ions ◽

Fermentation Products ◽

Ruminant Species ◽

Protective Shield ◽

Stratified Squamous Epithelium ◽

Lead Hydroxide ◽

Acetic Acids

The stratified squamous epithelium which lines the ruminal compartment of the bovine stomach performs at least three important functions. (1) The upper keratinized layer forms a protective shield against the rough, fibrous, constantly moving ingesta. (2) It is an organ of absorption since a number of substances are absorbed directly through the epithelium. These include short chain fatty acids, potassium, sodium and chloride ions, water, and many others. (3) The cells of the deeper layers metabolize butyric acid and to a lesser extent propionic and acetic acids which are the fermentation products of rumen digestion. Because of the functional characteristics, this epithelium is important in the digestive process of ruminant species which convert large quantities of rough, fibrous feed into energy.Tissue used in this study was obtained by biopsy through a rumen fistula from clinically healthy, yearling holstein steers. The animals had been fed a typical diet of hay and grain and the ruminal papillae were fully developed. The tissue was immediately immersed in 1% osmium tetroxide buffered to a pH of 7.4 and fixed for 2 hrs. The tissue blocks were embedded in Vestapol-W, sectioned with a Porter-Blum microtome with glass knives and stained with lead hydroxide. The sections were studied with an RCA EMU 3F electron microscope.

Download Full-text

EGCG modulates PKD1 and ferroptosis to promote recovery in ST rats

Translational Neuroscience ◽

10.1515/tnsci-2020-0119 ◽

2020 ◽

Vol 11 (1) ◽

pp. 173-181 ◽

Cited By ~ 1

Author(s):

Jianjun Wang ◽

Ying Chen ◽

Long Chen ◽

Yanzhi Duan ◽

Xuejun Kuang ◽

...

Keyword(s):

Spinal Cord ◽

Functional Recovery ◽

Antioxidant Properties ◽

Underlying Mechanism ◽

Maximal Effect ◽

Loss Of Function ◽

Protein Kinase D1 ◽

Erk Phosphorylation ◽

Cord Injury ◽

Novel Strategy

AbstractBackgroundSpinal cord injury (SCI) causes devastating loss of function and neuronal death without effective treatment. (−)-Epigallocatechin-3-gallate (EGCG) has antioxidant properties and plays an essential role in the nervous system. However, the underlying mechanism by which EGCG promotes neuronal survival and functional recovery in complete spinal cord transection (ST) remains unclear.MethodsIn the present study, we established primary cerebellar granule neurons (CGNs) and a T10 ST rat model to investigate the antioxidant effects of EGCG via its modulation of protein kinase D1 (PKD1) phosphorylation and inhibition of ferroptosis.ResultsWe revealed that EGCG significantly increased the cell survival rate of CGNs and PKD1 phosphorylation levels in comparison to the vehicle control, with a maximal effect observed at 50 µM. EGCG upregulated PKD1 phosphorylation levels and inhibited ferroptosis to reduce the cell death of CGNs under oxidative stress and to promote functional recovery and ERK phosphorylation in rats following complete ST.ConclusionTogether, these results lay the foundation for EGCG as a novel strategy for the treatment of SCI related to PKD1 phosphorylation and ferroptosis.

Download Full-text

Inner Ear and Muscle Developmental Defects in Smpx-Deficient Zebrafish Embryos

International Journal of Molecular Sciences ◽

10.3390/ijms22126497 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6497

Author(s):

Anna Ghilardi ◽

Alberto Diana ◽

Renato Bacchetta ◽

Nadia Santo ◽

Miriam Ascagni ◽

...

Keyword(s):

Hearing Loss ◽

Inner Ear ◽

Hair Cells ◽

Muscle Fibers ◽

Underlying Mechanism ◽

Loss Of Function ◽

Zebrafish Model ◽

Developmental Defects ◽

Inner Ear Development ◽

Syndromic Hearing Loss

The last decade has witnessed the identification of several families affected by hereditary non-syndromic hearing loss (NSHL) caused by mutations in the SMPX gene and the loss of function has been suggested as the underlying mechanism. In the attempt to confirm this hypothesis we generated an Smpx-deficient zebrafish model, pointing out its crucial role in proper inner ear development. Indeed, a marked decrease in the number of kinocilia together with structural alterations of the stereocilia and the kinocilium itself in the hair cells of the inner ear were observed. We also report the impairment of the mechanotransduction by the hair cells, making SMPX a potential key player in the construction of the machinery necessary for sound detection. This wealth of evidence provides the first possible explanation for hearing loss in SMPX-mutated patients. Additionally, we observed a clear muscular phenotype consisting of the defective organization and functioning of muscle fibers, strongly suggesting a potential role for the protein in the development of muscle fibers. This piece of evidence highlights the need for more in-depth analyses in search for possible correlations between SMPX mutations and muscular disorders in humans, thus potentially turning this non-syndromic hearing loss-associated gene into the genetic cause of dysfunctions characterized by more than one symptom, making SMPX a novel syndromic gene.

Download Full-text

Altered Expression of Peroxiredoxins in Mouse Model of Progressive Myoclonus Epilepsy upon LPS-Induced Neuroinflammation

Antioxidants ◽

10.3390/antiox10030357 ◽

2021 ◽

Vol 10 (3) ◽

pp. 357

Author(s):

Mojca Trstenjak Prebanda ◽

Petra Matjan-Štefin ◽

Boris Turk ◽

Nataša Kopitar-Jerala

Keyword(s):

Mouse Model ◽

Redox Homeostasis ◽

Underlying Mechanism ◽

Loss Of Function ◽

Altered Expression ◽

Lps Challenge ◽

Progressive Myoclonus Epilepsy ◽

Myoclonus Epilepsy ◽

The Brain ◽

Deficient Mice

Stefin B (cystatin B) is an inhibitor of endo-lysosomal cysteine cathepsin, and the loss-of-function mutations in the stefin B gene were reported in patients with Unverricht–Lundborg disease (EPM1), a form of progressive myoclonus epilepsy. Stefin B-deficient mice, a mouse model of the disease, display key features of EPM1, including myoclonic seizures. Although the underlying mechanism is not yet completely clear, it was reported that the impaired redox homeostasis and inflammation in the brain contribute to the progression of the disease. In the present study, we investigated if lipopolysaccharide (LPS)-triggered neuroinflammation affected the protein levels of redox-sensitive proteins: thioredoxin (Trx1), thioredoxin reductase (TrxR), peroxiredoxins (Prxs) in brain and cerebella of stefin B-deficient mice. LPS challenge was found to result in a marked elevation of Trx1 and TrxR in the brain and cerebella of stefin B deficient mice, while Prx1 was upregulated only in cerebella after LPS challenge. Mitochondrial peroxiredoxin 3 (Prx3), was upregulated also in the cerebellar tissue lysates prepared from unchallenged stefin B deficient mice, while after LPS challenge Prx3 was upregulated in stefin B deficient brain and cerebella. Our results imply the role of oxidative stress in the progression of the disease.

Download Full-text

miR-16-5p Promotes Erythroid Maturation of Erythroleukemia Cells by Regulating Ribosome Biogenesis

Pharmaceuticals ◽

10.3390/ph14020137 ◽

2021 ◽

Vol 14 (2) ◽

pp. 137

Author(s):

Christos I. Papagiannopoulos ◽

Nikoleta F. Theodoroula ◽

Ioannis S. Vizirianakis

Keyword(s):

Ribosomal Proteins ◽

Ribosome Biogenesis ◽

Cultured Cells ◽

Erythroid Differentiation ◽

Underlying Mechanism ◽

Loss Of Function ◽

Functional Studies ◽

Differentiated Cells ◽

Erythroleukemia Cells ◽

Murine Erythroleukemia

miRNAs constitute a class of non-coding RNA that act as powerful epigenetic regulators in animal and plant cells. In order to identify putative tumor-suppressor miRNAs we profiled the expression of various miRNAs during differentiation of erythroleukemia cells. RNA was purified before and after differentiation induction and subjected to quantitative RT-PCR. The majority of the miRNAs tested were found upregulated in differentiated cells with miR-16-5p showing the most significant increase. Functional studies using gain- and loss-of-function constructs proposed that miR-16-5p has a role in promoting the erythroid differentiation program of murine erythroleukemia (MEL) cells. In order to identify the underlying mechanism of action, we utilized bioinformatic in-silico platforms that incorporate predictions for the genes targeted by miR-16-5p. Interestingly, ribosome constituents, as well as ribosome biogenesis factors, were overrepresented among the miR-16-5p predicted gene targets. Accordingly, biochemical experiments showed that, indeed, miR-16-5p could modulate the levels of independent ribosomal proteins, and the overall ribosomal levels in cultured cells. In conclusion, miR-16-5p is identified as a differentiation-promoting agent in erythroleukemia cells, demonstrating antiproliferative activity, likely as a result of its ability to target the ribosomal machinery and restore any imbalanced activity imposed by the malignancy and the blockade of differentiation.

Download Full-text