Amelotin—a Novel Secreted, Ameloblast-specific Protein

2005 ◽  
Vol 84 (12) ◽  
pp. 1127-1132 ◽  
Author(s):  
K. Iwasaki ◽  
E. Bajenova ◽  
E. Somogyi-Ganss ◽  
M. Miller ◽  
V. Nguyen ◽  
...  
Keyword(s):  
Alveolar Bone ◽  
Bone Cells ◽  
Critical Role ◽  
Dental Enamel ◽  
Specific Protein ◽  
Pcr Analysis ◽  
Maturation Stage ◽  
Specific Gene ◽  
Tooth Formation ◽  
Dental Tissues

We aimed to analyze the differential gene expression in various murine dental tissues, expecting to find novel factors that are involved in tooth formation. We here describe the identification of a novel ameloblast-specific gene, amelotin (AMTN), by differential display polymerase chain-reaction (DD-PCR) analysis of microdissected ameloblasts, odontoblasts, dental pulp, and alveolar bone cells of 10-day-old mouse incisors. The conceptually translated protein sequence was unique and showed significant homology only with its human orthologue. The amelotin genes from mouse and human displayed a similar exon-intron structure and were expressed from loci on chromosomes 5 and 4, respectively, which have been associated with various forms of amelogenesis imperfecta. Expression of amelotin mRNA was restricted to maturation-stage ameloblasts in developing murine molars and incisors. Amelotin protein was efficiently secreted from transfected cells in culture. Taken together, our findings suggest that amelotin is a novel factor produced by ameloblasts that plays a critical role in the formation of dental enamel.

Abstract 82: Wnt11 Regulates Chamber Specific Neonatal Cardiomyocyte Proliferation During Perinatal Circulatory Transition

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Marlin Touma ◽  
Xuedong Kang ◽  
Fuying Gao ◽  
Yan Zhao ◽  
Reshma Biniwale ◽  
...  
Keyword(s):  
Heart Defects ◽  
Critical Role ◽  
Newborn Infants ◽  
R Package ◽  
Maturation Stage ◽  
Specific Gene ◽  
Mouse Heart ◽  
Cardiomyocyte Proliferation ◽  
Loss Of Function ◽  
Myocyte Proliferation

Background: Fetal to neonatal transition of heart involves major changes in cardiomyocytes (CMC) including proliferative capacity. However, the chamber specific CMC proliferation programs of remain poorly understood. Elucidating the mechanisms involved is critical to develop chamber specific therapies for newborn infants with single ventricle physiology and other congenital heart defects (CHDs). Methods: Transcriptomes of mouse left ventricle (LV) and right ventricle (RV) were analyzed by RNA-seq at postnatal days 0 (P0), P3 and P7. R package and Ingenuity suite were used for weighted gene co-expression network analysis (WGCNA) and gene ontology studies. Mechanistic analysis was conducted using gain and loss of function approaches. Results: Mouse neonatal cardiac transcriptome was mostly affected by developmental stage. WGCNA revealed 5 LV and 8 RV modules that were significantly correlated with maturation stage and highly preserved between both ventricles at P0 and P7. In contrast, P3 specific gene modules exhibited the largest chamber specific variations in cell signaling, involving proliferation in LV and Wnt signaling molecules, including Wnt11, in RV. Importantly, Wnt11 expression significantly decreased in cyanotic CHDs phenotypes and correlated with O2 saturation levels in hypoxemic infants with Tetralogy of Fallot (TOF). Notably, Perinatal hypoxia treatment in mice suppressed Wnt11 expression, induced CMC proliferation, downregulated Rb1 expression and enhanced Rb1 phosphorylation more robustly in RV vs. LV. Remarkably, Wnt11 inactivation was sufficient to induce myocyte proliferation in perinatal mouse heart and reduced Rb1 expression and phosphorylation in primary neonatal CMC. Importantly, downregulated Wnt11 in hypoxemic TOF infantile heart was also associated with Rb1 suppression and inversely correlated with proliferation marker Plk1 in human. Conclusion: Using integrated systems genomic and functional biology analyses of perinatal cardiac transcriptome, we revealed a previously uncharacterized function for Wnt11 in chamber specific growth and cyanotic CHD. Reduction of Wnt11 expression by hypoxia plays a critical role in neonatal CMC proliferation via modulating Rb1 expression and activity.

Maturation Stage-Specific Regulation of Megakaryocytic Genes by Pointed-Domain Ets Proteins.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1737-1737
Author(s):  
Liyan Pang ◽  
Xun Wang ◽  
Yuhuan Wang ◽  
Gerd Blobel ◽  
Mortimer Poncz
Keyword(s):  
Gene Expression ◽  
Fetal Liver ◽  
Critical Role ◽  
Regulatory Region ◽  
Maturation Stage ◽  
Specific Gene ◽  
Mrna Levels ◽  
Specific Regulation

Abstract The pointed-domain Ets transcription factor Fli-1 has a critical role during megakaryocyte-specific gene expression. Previously, we demonstrated that Fli-1 occupies the early megakaryocyte-specific gene αIIb in vivo. Moreover, our work suggested a mechanism for Fli-1 function by showing that Fli-1 facilitates GATA-1/FOG-1 dependent expression of the αIIb gene. However, studies by others with a targeted disruption of the Fli-1 gene in mice showed that while Fli-1 is essential for normal megakaryocyte maturation, αIIb mRNA levels were not significantly reduced in the resulting megakaryocytes, suggesting that a related Ets factor(s) might compensate for the loss of Fli-1. Here we show that the widely expressed pointed domain Ets protein GABPα specifically binds in vitro to Ets elements from two early megakaryocyte-specific genes, αIIb and c-mpl. Chromatin immunoprecipitation (ChIP) experiments using primary murine fetal liver-derived megakaryocytes reveal that GABPα associates with αIIb and c-mpl in vivo. Moreover, GABPα is capable of mediating GATA-1/FOG-1 synergy in the context of αIIb promoter constructs. These results suggest that GABPα contributes to megakaryocyte-restricted gene expression and is capable of at least partially compensating for the loss of Fli-1. However, loss of Fli-1 leads to a pronounced decrease in the expression of the late megakaryocyte-specific gene GPIX, indicating that compensation by GABPα is incomplete. Consistent with this observation, ChIP experiments fail to detect significant levels of GABPα at the regulatory region of GPIX while Fli-1 is readily detected there. Together, these results point to a model in which Fli-1 and GABPα serve overlapping, but distinct roles, during the development of megakaryocytes. GABPα may be important during early megakaryopoiesis, but Fli-1 exerting an essential role during late stages of maturation.

Scanning Electron Microscopy and X-Ray Analyses of Dental Tissues from a Hibernator

1976 ◽  
Vol 34 ◽  
pp. 178-179
Author(s):  
M. L. Zimny ◽  
A. C. Haller
Keyword(s):  
Electron Microscopy ◽  
Scanning Electron Microscopy ◽  
Body Temperature ◽  
Ground Squirrel ◽  
Alveolar Bone ◽  
X Ray ◽  
Dental Tissues ◽  
Bone Minerals ◽  
Apical Tooth ◽  
Scanning Electron

During hibernation the ground squirrel is immobile, body temperature reduced and metabolism depressed. Hibernation has been shown to affect dental tissues varying degrees, although not much work has been done in this area. In limited studies, it has been shown that hibernation results in (1) mobilization of bone minerals; (2) deficient dentinogenesis and degeneration of alveolar bone; (3) presence of calculus and tears in the cementum; and (4) aggrevation of caries and pulpal and apical tooth abscesses. The purpose of this investigation was to study the effects of hibernation on dental tissues employing scanning electron microscopy (SEM) and related x-ray analyses.

DETECTION OF RESIDUAL LUNG CANCER CELLS BY PCR-BASED GENETIC TESTING FOR ROS1-TRANSLOCATION: CASE REPORT

2018 ◽  
Vol 64 (3) ◽  
pp. 331-334
Author(s):  
Fedor Moiseenko ◽  
Vladislav Tyurin ◽  
Nikita Levchenko ◽  
Yevgeniy Levchenko ◽  
Aglaya Ievleva ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Morphological Analysis ◽  
Pathologic Complete Response ◽  
Residual Tumor ◽  
Complete Response ◽  
Convincing Evidence ◽  
Pcr Analysis ◽  
Specific Gene ◽  
Highly Sensitive ◽  
Reliable Monitoring

A patient with lung cancer carrying ROS1 translocation was treated by crizotinib and then subjected to surgery. Morphological analysis revealed pathologic complete response in surgically removed tissues, while PCR test provided convincing evidence for the presence of residual tumor cells. PCR analysis of lung cancer specific gene translocations allows carrying out highly sensitive and reliable monitoring of tumor disease during the course of treatment.

Bone Invasive Properties of Oral Squamous Cell Carcinoma and its Interactions with Alveolar Bone Cells: An In Vitro Study

2019 ◽  
Vol 19 (8) ◽  
pp. 631-640 ◽  
Author(s):  
Omel Baneen Qallandar ◽  
Faeza Ebrahimi ◽  
Farhadul Islam ◽  
Riajul Wahab ◽  
Bin Qiao ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Cells ◽  
Alveolar Bone ◽  
Cultured Cells ◽  
Bone Cells ◽  
Bone Invasion ◽  
Alveolar Bone Cells

Background: Co-culture of cancer cells with alveolar bone cells could modulate bone invasion and destructions. However, the mechanisms of interaction between oral squamous cell carcinoma (OSCC) and bone cells remain unclear. Objective: The aim of this study is to analyse the direct and indirect effects of OSCC cells in the stimulation of osteolytic activity and bone invasion. Methods: Direct co-culture was achieved by culturing OSCC (TCA8113) with a primary alveolar bone cell line. In the indirect co-culture, the supernatant of TCA8113 cells was collected to culture the alveolar bone cells. To assess the bone invasion properties, in vitro assays were performed. Results: The proliferation of co-cultured cancer cells was significantly (p<0.05) higher in comparison to the monolayer control cells. However, the proliferation rates were not significantly different between direct and indirect co-cultured cells with indirect co-cultured cells proliferated slightly more than the direct co-cultured cells. Invasion and migration capacities of co-cultured OSCC and alveolar bone cells enhanced significantly (p<0.05) when compared to that of control monolayer counterparts. Most importantly, we noted that OSCC cells directly co-cultured with alveolar bone cells stimulated pronounced bone collagen destruction. In addition, stem cells and epithelialmesenchymal transition markers have shown significant changes in their expression in co-cultured cells. Conclusion: In conclusion, the findings of this study highlight the importance of the interaction of alveolar bone cells and OSCC cells in co-culture setting in the pathogenesis of bone invasion. This may help in the development of potential future biotherapies for bone invasion in OSCC.

scholarly journals Renal Proximal Tubule Cell Cannabinoid-1 Receptor Regulates Bone Remodeling and Mass via a Kidney-to-Bone Axis

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 414
Author(s):  
Saja Baraghithy ◽  
Yael Soae ◽  
Dekel Assaf ◽  
Liad Hinden ◽  
Shiran Udi ◽  
...  
Keyword(s):  
Bone Mass ◽  
Proximal Tubule ◽  
Bone Remodeling ◽  
Kidney Function ◽  
Bone Cells ◽  
Critical Role ◽  
Renal Proximal Tubule ◽  
Proximal Tubule Cell ◽  
Protective Effects ◽  
Cannabinoid 1 Receptor

The renal proximal tubule cells (RPTCs), well-known for maintaining glucose and mineral homeostasis, play a critical role in the regulation of kidney function and bone remodeling. Deterioration in RPTC function may therefore lead to the development of diabetic kidney disease (DKD) and osteoporosis. Previously, we have shown that the cannabinoid-1 receptor (CB1R) modulates both kidney function as well as bone remodeling and mass via its direct role in RPTCs and bone cells, respectively. Here we employed genetic and pharmacological approaches that target CB1R, and found that its specific nullification in RPTCs preserves bone mass and remodeling both under normo- and hyper-glycemic conditions, and that its chronic blockade prevents the development of diabetes-induced bone loss. These protective effects of negatively targeting CB1R specifically in RPTCs were associated with its ability to modulate erythropoietin (EPO) synthesis, a hormone known to affect bone mass and remodeling. Our findings highlight a novel molecular mechanism by which CB1R in RPTCs remotely regulates skeletal homeostasis via a kidney-to-bone axis that involves EPO.

scholarly journals Endurance Training Regulates Expression of Some Angiogenesis-Related Genes in Cardiac Tissue of Experimentally Induced Diabetic Rats

Biomolecules ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 498
Author(s):  
Mojdeh Khajehlandi ◽  
Lotfali Bolboli ◽  
Marefat Siahkuhian ◽  
Mohammad Rami ◽  
Mohammadreza Tabandeh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endurance Training ◽  
Molecular Mechanisms ◽  
Cardiac Tissue ◽  
Critical Role ◽  
Diabetic Rats ◽  
Moderate Intensity ◽  
Pcr Analysis ◽  
Cardiac Tissues ◽  
The Impact

Exercise can ameliorate cardiovascular dysfunctions in the diabetes condition, but its precise molecular mechanisms have not been entirely understood. The aim of the present study was to determine the impact of endurance training on expression of angiogenesis-related genes in cardiac tissue of diabetic rats. Thirty adults male Wistar rats were randomly divided into three groups (N = 10) including diabetic training (DT), sedentary diabetes (SD), and sedentary healthy (SH), in which diabetes was induced by a single dose of streptozotocin (50 mg/kg). Endurance training (ET) with moderate-intensity was performed on a motorized treadmill for six weeks. Training duration and treadmill speed were increased during five weeks, but they were kept constant at the final week, and slope was zero at all stages. Real-time polymerase chain reaction (RT-PCR) analysis was used to measure the expression of myocyte enhancer factor-2C (MEF2C), histone deacetylase-4 (HDAC4) and Calmodulin-dependent protein kinase II (CaMKII) in cardiac tissues of the rats. Our results demonstrated that six weeks of ET increased gene expression of MEF2C significantly (p < 0.05), and caused a significant reduction in HDAC4 and CaMKII gene expression in the DT rats compared to the SD rats (p < 0.05). We concluded that moderate-intensity ET could play a critical role in ameliorating cardiovascular dysfunction in a diabetes condition by regulating the expression of some angiogenesis-related genes in cardiac tissues.

scholarly journals Halofuginone functions as a therapeutic drug for chronic periodontitis in a mouse model

2020 ◽  
Vol 34 ◽  
pp. 205873842097489
Author(s):  
Jiang Wang ◽  
Bo Wang ◽  
Xin Lv ◽  
Yingjie Wang
Keyword(s):  
Alveolar Bone ◽  
Immune Cell ◽  
Critical Role ◽  
Therapeutic Drug ◽  
Mice Model ◽  
T Helper 17 ◽  
Th17 Cell Differentiation ◽  
Tnf Α

Periodontitis is an inflammatory disease caused by host immune response, resulting in a loss of periodontium and alveolar bone. Immune cells, such as T cells and macrophages, play a critical role in the periodontitis onset. Halofuginone, a natural quinazolinone alkaloid, has been shown to possess anti-fibrosis, anti-cancer, and immunomodulatory properties. However, the effect of halofuginone on periodontitis has never been reported. In this study, a ligature-induced mice model of periodontitis was applied to investigate the potential beneficial effect of halofuginone on periodontitis. We demonstrated that the administration of halofuginone significantly reduced the expression levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) in vivo, and markedly suppressed immune cell infiltration into the infected sites. Furthermore, we also observed that halofuginone treatment blocked the T-helper 17 (Th17) cell differentiation in vivo and in vitro. We demonstrated for the first time that halofuginone alleviated the onset of periodontitis through reducing immune responses.

scholarly journals Role of Innate Inflammation in the Regulation of Tissue Remodeling during Tooth Eruption

2021 ◽  
Vol 9 (1) ◽  
pp. 7
Author(s):  
Yusuke Makino ◽  
Kaoru Fujikawa ◽  
Miwako Matsuki-Fukushima ◽  
Satoshi Inoue ◽  
Masanori Nakamura
Keyword(s):  
Bacterial Infections ◽  
Tooth Movement ◽  
Tooth Eruption ◽  
Intercellular Adhesion Molecule ◽  
Enamel Organ ◽  
Pcr Analysis ◽  
Maturation Stage ◽  
Oral Epithelium ◽  
Rt Pcr ◽  
Inflammatory Reactions

Tooth eruption is characterized by a coordinated complex cascade of cellular and molecular events that promote tooth movement through the eruptive pathway. During tooth eruption, the stratum intermedium structurally changes to the papillary layer with tooth organ development. We previously reported intercellular adhesion molecule-1 (ICAM-1) expression on the papillary layer, which is the origin of the ICAM-1-positive junctional epithelium. ICAM-1 expression is induced by proinflammatory cytokines, including interleukin-1 and tumor necrosis factor. Inflammatory reactions induce tissue degradation. Therefore, this study aimed to examine whether inflammatory reactions are involved in tooth eruption. Reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed sequential expression of hypoxia-induced factor-1α, interleukin-1β, and chemotactic factors, including keratinocyte-derived chemokine (KC) and macrophage inflammatory protein-2 (MIP-2), during tooth eruption. Consistent with the RT-PCR results, immunohistochemical analysis revealed KC and MIP-2 expression in the papillary layer cells of the enamel organ from the ameloblast maturation stage. Moreover, there was massive macrophage and neutrophil infiltration in the connective tissue between the tooth organ and oral epithelium during tooth eruption. These findings suggest that inflammatory reactions might be involved in the degradation of tissue overlying the tooth organ. Further, these reactions might be induced by hypoxia in the tissue overlying the tooth organ, which results from decreased capillaries in the tissue. Our findings indicate that bacterial infections are not associated with the eruption process. Therefore, tooth eruption might be regulated by innate inflammatory mechanisms.

scholarly journals Prostatic Acid Phosphatase Alters the RANKL/OPG System and Induces Osteoblastic Prostate Cancer Bone Metastases

Endocrinology ◽  
2016 ◽  
Vol 157 (12) ◽  
pp. 4526-4533 ◽  
Author(s):  
Alexander Kirschenbaum ◽  
Sudeh Izadmehr ◽  
Shen Yao ◽  
Kieley L. O’Connor-Chapman ◽  
Alan Huang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Acid Phosphatase ◽  
Bone Metastases ◽  
Cross Talk ◽  
Bone Cells ◽  
Bone Mineralization ◽  
Critical Role ◽  
Prostatic Acid Phosphatase ◽  
Bone Lesions ◽  
Rankl Expression

Prostate cancer (PCa) is unique in its tendency to produce osteoblastic (OB) bone metastases. There are no existing therapies that specifically target the OB phase that affects 90% of men with bone metastatic disease. Prostatic acid phosphatase (PAP) is secreted by PCa cells in OB metastases and increases OB growth, differentiation, and bone mineralization. The purpose of this study was to investigate whether PAP effects on OB bone metastases are mediated by autocrine and/or paracrine alterations in the receptor activator of nuclear factor κ-B (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system. To investigate whether PAP modulated these factors and altered the bone reaction, we knocked down PAP expression in VCaP cells and stably overexpressed PAP in PC3M cells, both derived from human PCa bone metastases. We show that knockdown of PAP in VCaP cells decreased OPG while increasing RANK/RANKL expression. Forced overexpression of PAP in PC3M cells had the inverse effect, increasing OPG while decreasing RANK/RANKL expression. Coculture of PCa cells with MC3T3 preosteoblasts also revealed a role for secretory PAP in OB-PCa cross talk. Reduced PAP expression in VCaP cells decreased MC3T3 proliferation and differentiation and reduced their OPG expression. PAP overexpression in PC3M cells altered the bone phenotype creating OB rather than osteolytic lesions in vivo using an intratibial model. These findings demonstrate that PAP secreted by PCa cells in OB bone metastases increases OPG and plays a critical role in the vicious cross talk between cancer and bone cells. These data suggest that inhibition of secretory PAP may be an effective strategy for PCa OB bone lesions.

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