Wnt signaling acts and is regulated in a human osteoblast differentiation dependent manner

2008 ◽  
Vol 104 (2) ◽  
pp. 568-579 ◽  
Author(s):  
M. Eijken ◽  
I.M.J. Meijer ◽  
I. Westbroek ◽  
M. Koedam ◽  
H. Chiba ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Osteoblast Differentiation ◽  
Dependent Manner ◽  
Human Osteoblast

scholarly journals Regulation of Wnt Signaling by FOX Transcription Factors in Cancer

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3446
Author(s):  
Stefan Koch
Keyword(s):  
Transcription Factors ◽  
Wnt Signaling ◽  
Wnt Pathway ◽  
Treatment Options ◽  
Wnt Signaling Pathway ◽  
Tissue Homeostasis ◽  
Fine Tuning ◽  
Dependent Manner ◽  
Forkhead Box ◽  
Signaling Activity

Aberrant activation of the oncogenic Wnt signaling pathway is a hallmark of numerous types of cancer. However, in many cases, it is unclear how a chronically high Wnt signaling tone is maintained in the absence of activating pathway mutations. Forkhead box (FOX) family transcription factors are key regulators of embryonic development and tissue homeostasis, and there is mounting evidence that they act in part by fine-tuning the Wnt signaling output in a tissue-specific and context-dependent manner. Here, I review the diverse ways in which FOX transcription factors interact with the Wnt pathway, and how the ectopic reactivation of FOX proteins may affect Wnt signaling activity in various types of cancer. Many FOX transcription factors are partially functionally redundant and exhibit a highly restricted expression pattern, especially in adults. Thus, precision targeting of individual FOX proteins may lead to safe treatment options for Wnt-dependent cancers.

scholarly journals The transcription factor osterix (SP7) regulates BMP6-induced human osteoblast differentiation

2012 ◽  
Vol 227 (6) ◽  
pp. 2677-2685 ◽  
Author(s):  
Fengchang Zhu ◽  
Michael S. Friedman ◽  
Weijun Luo ◽  
Peter Woolf ◽  
Kurt D. Hankenson
Keyword(s):  
Transcription Factor ◽  
Osteoblast Differentiation ◽  
Human Osteoblast

scholarly journals Small molecule T63 suppresses osteoporosis by modulating osteoblast differentiation via BMP and WNT signaling pathways

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Xiao-li Zhao ◽  
Jin-jing Chen ◽  
Guo-ning Zhang ◽  
Yu-cheng Wang ◽  
Shu-yi Si ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathways ◽  
Small Molecule ◽  
Osteoblast Differentiation

Fatty acids and cytokine mRNA expression in human osteoblastic cells: a specific effect of arachidonic acid

2002 ◽  
Vol 102 (4) ◽  
pp. 403-409 ◽  
Author(s):  
G. PRIANTE ◽  
L. BORDIN ◽  
E. MUSACCHIO ◽  
G. CLARI ◽  
B. BAGGIO
Keyword(s):  
Fatty Acids ◽  
Arachidonic Acid ◽  
Mrna Expression ◽  
Specific Effect ◽  
Significant Inhibition ◽  
Cytokine Gene Expression ◽  
Dependent Manner ◽  
Human Osteoblast ◽  
Cytokine Mrna ◽  
Cytokine Mrna Expression

Epidemiological, clinical and experimental evidence suggests that fatty acids have a modulatory effect on bone metabolism in animals and humans. To investigate this hypothesis, we evaluated the effects of three different fatty acids, arachidonic acid (AA), eicosapentaenoic acid (EPA) and oleic acid (OA), on the expression of cytokines involved in bone remodelling. Cytokine mRNAs in the human osteoblast-like cell line MG-63 were quantified by reverse transcription-PCR. AA induced increased expression of interleukin-1α, interleukin-1β, tumour necrosis factor-α and macrophage colony-stimulating factor mRNAs in a time- and dose-dependent manner. EPA and OA had no stimulatory effects, but instead caused a significant inhibition of AA-induced cytokine mRNA expression. Cell treatment with calphostin C, an inhibitor of protein kinase C (PKC), and cellular PKC down-regulation experiments independently resulted in significant inhibition of AA-induced cytokine expression, suggesting that a PKC-dependent mechanism accounts for the effects of AA on cytokine production. In conclusion, our study demonstrates specific effects of fatty acids on cytokine gene expression in human osteoblast-like cells. The clinical relevance of our findings requires further investigation.

scholarly journals Maternal Wnt/STOP signaling promotes cell division during earlyXenopusembryogenesis

2015 ◽  
Vol 112 (18) ◽  
pp. 5732-5737 ◽  
Author(s):  
Ya-Lin Huang ◽  
Zeinab Anvarian ◽  
Gabriele Döderlein ◽  
Sergio P. Acebron ◽  
Christof Niehrs
Keyword(s):  
Wnt Signaling ◽  
Cell Cycle Progression ◽  
Glycogen Synthase ◽  
Effector Proteins ◽  
Glycogen Synthase Kinase 3 ◽  
Dependent Manner ◽  
Early Cleavage ◽  
Cycle Progression ◽  
Midblastula Transition ◽  
Axial Patterning

DuringXenopusdevelopment, Wnt signaling is thought to function first after midblastula transition to regulate axial patterning via β-catenin–mediated transcription. Here, we report that Wnt/glycogen synthase kinase 3 (GSK3) signaling functions posttranscriptionally already in mature oocytes via Wnt/stabilization of proteins (STOP) signaling. Wnt signaling is induced in oocytes after their entry into meiotic metaphase II and declines again upon exit into interphase. Wnt signaling inhibits Gsk3 and thereby protects proteins from polyubiquitination and degradation in mature oocytes. In a protein array screen, we identify a cluster of mitotic effector proteins that are polyubiquitinated in a Gsk3-dependent manner inXenopus. Consequently inhibition of maternal Wnt/STOP signaling, but not β-catenin signaling, leads to early cleavage arrest after fertilization. The results support a novel role for Wnt signaling in cell cycle progression independent of β-catenin.

scholarly journals Epigenomic landscape of enhancer elements during Hydra head organizer formation

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Puli Chandramouli Reddy ◽  
Akhila Gungi ◽  
Suyog Ubhe ◽  
Sanjeev Galande
Keyword(s):  
Gene Expression ◽  
Wnt Signaling ◽  
Histone Modifications ◽  
Specific Inhibitor ◽  
Regulatory Elements ◽  
The Body ◽  
Luciferase Reporter ◽  
Dependent Manner ◽  
Chromatin Architecture ◽  
Ectopic Activation

Abstract Background Axis patterning during development is accompanied by large-scale gene expression changes. These are brought about by changes in the histone modifications leading to dynamic alterations in chromatin architecture. The cis regulatory DNA elements also play an important role towards modulating gene expression in a context-dependent manner. Hydra belongs to the phylum Cnidaria where the first asymmetry in the body plan was observed and the oral-aboral axis originated. Wnt signaling has been shown to determine the head organizer function in the basal metazoan Hydra. Results To gain insights into the evolution of cis regulatory elements and associated chromatin signatures, we ectopically activated the Wnt signaling pathway in Hydra and monitored the genome-wide alterations in key histone modifications. Motif analysis of putative intergenic enhancer elements from Hydra revealed the conservation of bilaterian cis regulatory elements that play critical roles in development. Differentially regulated enhancer elements were identified upon ectopic activation of Wnt signaling and found to regulate many head organizer specific genes. Enhancer activity of many of the identified cis regulatory elements was confirmed by luciferase reporter assay. Quantitative chromatin immunoprecipitation analysis upon activation of Wnt signaling further confirmed the enrichment of H3K27ac on the enhancer elements of Hv_Wnt5a, Hv_Wnt11 and head organizer genes Hv_Bra1, CnGsc and Hv_Pitx1. Additionally, perturbation of the putative H3K27me3 eraser activity using a specific inhibitor affected the ectopic activation of Wnt signaling indicating the importance of the dynamic changes in the H3K27 modifications towards regulation of the genes involved in the head organizer activity. Conclusions The activation-associated histone marks H3K4me3, H3K27ac and H3K9ac mark chromatin in a similar manner as seen in bilaterians. We identified intergenic cis regulatory elements which harbor sites for key transcription factors involved in developmental processes. Differentially regulated enhancers exhibited motifs for many zinc-finger, T-box and ETS related TFs whose homologs have a head specific expression in Hydra and could be a part of the pioneer TF network in the patterning of the head. The ability to differentially modify the H3K27 residue is critical for the patterning of Hydra axis revealing a dynamic acetylation/methylation switch to regulate gene expression and chromatin architecture.

scholarly journals Osteoblast differentiation of NIH3T3 fibroblasts is associated with changes in the IGF-I/IGFBP expression pattern

2006 ◽  
Vol 11 (4) ◽  
Author(s):  
Basem Abdallah
Keyword(s):  
Cell Line ◽  
Expression Pattern ◽  
Osteoblast Differentiation ◽  
Culture Conditions ◽  
Time Dependent ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Igf Binding Proteins ◽  
Igf System ◽  
Igf I

AbstractInsulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) are essential regulators for osteoblast proliferation and differentiation. It has been reported that Dexamethasone (Dex), an active glucocorticoid (GC) analogue, synergizes the stimulatory effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on osteoblast differentiation in the mouse fibroblastic cell line NIH3T3. I investigated whether this stimulatory effect is associated with changes in the expression pattern of the IGF/IGFBP system. Quantitative real-time PCR technology was used to quantify the gene expression levels of the IGF-system during osteoblast differentiation and in response to 1,25(OH)2D3 or Dex alone under serum-containing and serum-free culture conditions. Interestingly, NIH3T3 was shown to express high mRNA levels of IGF-I, IGF-II and IGFBP-5, and low levels of both IGFBP-2 and-6. During osteoblast differentiation (days 6-12), IGF-I mRNA was repressed by more than 60%, while the transcript of IGFBP-5 was markedly up-regulated, by more than 50-fold. Similarly, treatment with Dex alone resulted in a dose-and time-dependent increase in the expression of IGFBP-5 and a decrease in IGF-I mRNA. Treatment with 1,25(OH)2D3 alone increased the mRNA levels of IGF-I and IGFBP-6 by around 4-and 7-fold, respectively, in a dose-and time-dependent manner. In conclusion, my data demonstrated that osteoblast differentiation of NIH3T3 is associated with changes in the expression pattern of IGFs/IGFBPs, which are regulated by glucocorticoid in the presence of 1,25(OH)2D3. Modulation of the IGF/IGFBP levels by glucocorticoid might suggest important roles for the IGF-system in mediating the osteoblast differentiation of the NIH3T3 cell line.

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