Document Detail

TGF-beta1 inhibits multiple caspases induced by TNF-alpha in murine osteoblastic MC3T3-E1 cells.
MedLine Citation:
PMID:  12431778     Owner:  NLM     Status:  MEDLINE    
Tumor necrosis factor alpha (TNF-alpha) is a proinflammatory cytokine that induces apoptosis in a number of cell systems, including osteoblasts. Transforming growth factor beta1 (TGF-beta1) is an abundant growth factor that is known to stimulate bone formation. This study was designed to examine the role of TGF-beta1 on TNF-alpha-induced apoptosis in murine osteoblastic MC3T3-E1 cells. Total RNA was extracted from MC3T3-E1 cells treated with 20 ng/ml of TNF-alpha, 10 ng/ml of TGF-beta1, or combination, for 6 h. TNF-alpha exerted a variety of effects on the apoptotic gene expression in osteoblasts. Ribonuclease protection assays (RPA) revealed that TNF-alpha upregulated the mRNA levels of caspase-1, -7, -11, -12, and FAS. Western blot analysis showed enhanced processing of caspase-1, -7, -11, and -12, with the appearance of their activated enzymes 24 h after TNF-alpha treatment. In addition, caspase-3-like activity was significantly activated following TNF-alpha treatment. Levels of cleaved poly(ADP-ribose) polymerase and FAS protein were also elevated by TNF-alpha. Finally, Hoechst staining, terminal deoxynucleotidyl-transferase nick-end labeling (TUNEL) assay, and oligonucleosome ELISA all indicated that TNF-alpha induced apoptosis. In contrast, the addition of TGF-beta1 attenuated all of the aforementioned effects of TNF-alpha. Our results demonstrate that TGF-beta1 can decrease TNF-alpha-induced apoptosis in murine osteoblasts at least in part by attenuating TNF-alpha-induced caspase gene expression.
Chu Chang Chua; Balvin H L Chua; Zhongyi Chen; Cathy Landy; Ronald C Hamdy
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1593     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2002 Dec 
Date Detail:
Created Date:  2002-11-14     Completed Date:  2003-02-27     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1-8     Citation Subset:  IM    
Copyright Information:
Copyright 2002 Elsevier Science B.V.
Osteoporosis Center, James H Quillen College of Medicine, East Tennessee State University, and Veterans Affairs Medical Center, Box 70432, Johnson City, TN 37614, USA.
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MeSH Terms
Apoptosis / genetics
Caspases / metabolism*
Enzyme-Linked Immunosorbent Assay
Fluorescent Dyes
In Situ Nick-End Labeling
Osteoblasts / enzymology*
Receptors, Tumor Necrosis Factor / metabolism
Recombinant Proteins / genetics,  metabolism
Transforming Growth Factor beta / genetics,  metabolism*,  pharmacology
Transforming Growth Factor beta1
Tumor Necrosis Factor-alpha / genetics,  metabolism*,  pharmacology
Reg. No./Substance:
0/Fluorescent Dyes; 0/Receptors, Tumor Necrosis Factor; 0/Recombinant Proteins; 0/Tgfb1 protein, mouse; 0/Transforming Growth Factor beta; 0/Transforming Growth Factor beta1; 0/Tumor Necrosis Factor-alpha; 23491-44-3/Bisbenzimidazole; EC 3.4.22.-/Caspases

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