scholarly journals Bisphosphonates regulate cell growth and gene expression in the UMR 106-01 clonal rat osteosarcoma cell line

2001 ◽  
Vol 84 (7) ◽  
pp. 951-958 ◽  
Author(s):  
P S Mackie ◽  
J L Fisher ◽  
H Zhou ◽  
P F M Choong
Author(s):  
Paweł Marek Majewski ◽  
Urszula Kędzierska ◽  
Łukasz Banasiak ◽  
Paweł Kiela

Although loss of bone mineral density is a common symptom of chronic inflammatory diseases, its mechanisms are still poorly understood. The PHEX gene encodes a Zn-endopeptidase expressed in osteoblasts and contributes to bone mineralization. Data derived from rodents has indicated co-repression of the PHEX gene by the NF-κB pathway and poly(ADP-ribose) polymerase 1 (PARP1). The aim of this study was to determine the molecular mechanism involved in TNF-mediated downregulation of PHEX expression in human osteoblasts and human osteosarcoma cell line. We observed that activation of the NF-κB pathway by TNF was manifested as a nuclear increase in RELA and NFKB1 heterodimer. We found that TNF reduced PHEX expression and the proteasome inhibitor reversed this effect in osteosarcoma cell line. Contrary to the effects seen in rodents, inhibition of PARP1 enzymatic activity did not significantly reverse the effect of TNF on the human PHEX gene expression. EMSA studies showed that the number of adenines in the PHEX proximal promoter is crucial for the transcription factors’ interactions within that region. The obtained results support the hypothesis indicating the existence of a molecular mechanism of gene repression that involves a poly adenine-rich region of the proximal gene promoters and PARP1 transcriptional activity.


1992 ◽  
Vol 12 (3) ◽  
pp. 207-214 ◽  
Author(s):  
Östen Ljunggren ◽  
Hans Johansson ◽  
Ulf H. Lerner ◽  
Erik Lindh ◽  
Sverker Ljunghall

The effects of parathyroid hormone (PTH) on cytoplasmic free CA2+ (Cai2+) and cAMP-formation were investigated in the rat osteosarcoma cell line UMR 106-01. In fura-2 loaded adherent single cells bPTH 1–34 (10 nM−1μM) induced a rapid transient increase in Cai2+ in 11% of the studied cells. In fura-2 tracings from UMR 106-01 cells in suspension, bPTH 1–34 (0.1 μM) induced a transient increase in Cai2+ in 20% of the experiments. The transient increase in Cai2+ seen in suspensions of cells was not abolished by addition of EGTA (2.5 mM) prior to challenge with PTH, suggesting that the increase in Cai2+ was derived from intracellular stores. A marked rapid increase in cAMP-formation was observed in all experiments with cells in suspension, also in the experiments where PTH did not affect Cai2+. These data show that PTH causes a release of Ca2+ from intracellular stores in a small percentage of osteosarcoma UMR 106-01 cells, and that PTH is capable of inducing an increase in cAMP-formation without affecting Cai2+ in osteoblasts.


2014 ◽  
Vol 8 (1) ◽  
pp. 127-132 ◽  
Author(s):  
PENG ZHANG ◽  
LING DONG ◽  
HUA LONG ◽  
TONG-TAO YANG ◽  
YONG ZHOU ◽  
...  

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