1α,25-Dihydroxyvitamin D3Increases Transforming Growth Factor and Transforming Growth Factor Receptor Type I and II Synthesis in Human Bone Cells

1997 ◽  
Vol 239 (3) ◽  
pp. 734-739 ◽  
Author(s):  
Yanhong Wu ◽  
James D. Haugen ◽  
Alan R. Zinsmeister ◽  
Rajiv Kumar
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Bone Cells ◽  
Growth Factor Receptor ◽  
Human Bone ◽  
Receptor Type ◽  
Type I ◽  
Transforming Growth Factor Receptor

Analysis of Transforming Growth Factor Receptor Type II in Patients with Agnogenic Myeloid Metaplasia (AMM).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4753-4753
Author(s):  
Kirugaval C. Hemavathy ◽  
Allan D. Novetsky ◽  
Jen C. Wang
Keyword(s):  
Growth Factor ◽  
Promoter Region ◽  
Genomic Dna ◽  
Transforming Growth Factor ◽  
Growth Factor Receptor ◽  
Receptor Type ◽  
Type Ii ◽  
Hdac Activity ◽  
Cd34 Cells ◽  
Transforming Growth Factor Receptor

Abstract We previously reported that blood TIMP-1 (Tissue Inhibitor of Metalloproteinase), OPG (Osteoprotegerin), and TPO (Thrombopoietin) levels are increased and blood MMP-3, and bone marrow SDF-1 levels are decreased in patients with AMM. Enhanced TGF-ß 1 activity with Transforming Growth Factor Receptor Type II (TGF ß RII) abnormalities is likely to be associated with these findings. It has been previously reported that TGF-ß RII levels are decreased in AMM patients. The current study was undertaken to explore the defects in the TGF-ß1 pathway in this disease. We cloned and sequenced the full length TGF ß RII cDNA from AMM patients and no mutations were detected on sequencing. We then determined the expression levels of TGF ß RII in the CD34+ progenitor cells by Real-Time RT-PCR and found it to be reduced in patients with AMM compared to normal volunteer CD34+ cells used as controls. Hence we cloned the promoter region of TGF ß RII (−1233 to +50) from the genomic DNA of Peripheral Blood Monocytes by PCR, using gene specific primers. On sequencing, no mutations were detected in the promoter regions. The same promoter region when cloned upstream of a luciferase gene, drove the transcription of the reporter gene similar to the levels observed with the promoter from controls. This augmented the absence of any structural abnormalities in the region of the TGF b RII promoter. We then analyzed the methylation status of TGF ß RII promoter using the technique, Sodium Bisulfite-PCR for Sequencing. Genomic DNA was modified using Sodium Bisulfite and the TGF ß RII promoter was amplified by PCR with Primers capable of amplifying both unmethylated and methylated DNA. The modified PCR products were cloned into TOPO TA sequencing vector from Invitrogen, CA and sequenced. The sequencing results revealed absence of any CpG hyper-methylation in the promoter region of TGF ß RII. To account for reduced TGF ß RII expression in the absence of coding region abnormalities, promoter abnormalities or hypermethylation, we determined Histone Deacetylase Activity HDAC activity in the CD34+ cells of AMM patients. There was an indirect correlation between HDAC activity and TGF ß RII mRNA levels implying HDAC mediated silencing of the TGF ß RII promoter in AMM patients.

scholarly journals Myostatin regulates the production of fibroblast growth factor 23 (FGF23) in UMR106 osteoblast–like cells

2021 ◽  
Author(s):  
Franz Ewendt ◽  
Martina Feger ◽  
Michael Föller
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Transforming Growth Factor ◽  
Bone Cells ◽  
Fibroblast Growth Factor 23 ◽  
Receptor Type ◽  
Type I ◽  
Fibroblast Growth ◽  
Activin Receptor

AbstractMyostatin is a signaling molecule produced by skeletal muscle cells (myokine) that inhibits muscle hypertrophy and has further paracrine and endocrine effects in other organs including bone. Myostatin binds to activin receptor type 2B which forms a complex with transforming growth factor-β type I receptor (TGF-βRI) and induces intracellular p38MAPK and NFκB signaling. Fibroblast growth factor 23 (FGF23) is a paracrine and endocrine mediator produced by bone cells and regulates phosphate and vitamin D metabolism in the kidney. P38MAPK and NFκB-dependent store-operated Ca2+ entry (SOCE) are positive regulators of FGF23 production. Here, we explored whether myostatin influences the synthesis of FGF23. Fgf23 gene expression was determined by qRT-PCR and FGF23 protein by ELISA in UMR106 osteoblast–like cells. UMR106 cells expressed activin receptor type 2A and B. Myostatin upregulated Fgf23 gene expression and protein production. The myostatin effect on Fgf23 was significantly attenuated by TGF-βRI inhibitor SB431542, p38MAPK inhibitor SB202190, and NFκB inhibitor withaferin A. Moreover, SOCE inhibitor 2-APB blunted the myostatin effect on Fgf23. Taken together, myostatin is a stimulator of Fgf23 expression in UMR106 cells, an effect at least partially mediated by downstream TGF-βRI/p38MAPK signaling as well as NFκB-dependent SOCE.

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