TGF-β1 Inhibits Multiple Caspases Induced by TNF-α in Murine Osteoblastic MC3T3-E1 Cells
Document Type
Article
Publication Date
12-16-2002
Description
Tumor necrosis factor α (TNF-α) is a proinflammatory cytokine that induces apoptosis in a number of cell systems, including osteoblasts. Transforming growth factor β1 (TGF-β1) is an abundant growth factor that is known to stimulate bone formation. This study was designed to examine the role of TGF-β1 on TNF-α-induced apoptosis in murine osteoblastic MC3T3-E1 cells. Total RNA was extracted from MC3T3-E1 cells treated with 20 ng/ml of TNF-α, 10 ng/ml of TGF-β1, or combination, for 6 h. TNF-α exerted a variety of effects on the apoptotic gene expression in osteoblasts. Ribonuclease protection assays (RPA) revealed that TNF-α 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-α treatment. In addition, caspase-3-like activity was significantly activated following TNF-α treatment. Levels of cleaved poly(ADP-ribose) polymerase and FAS protein were also elevated by TNF-α. Finally, Hoechst staining, terminal deoxynucleotidyl-transferase nick-end labeling (TUNEL) assay, and oligonucleosome ELISA all indicated that TNF-α induced apoptosis. In contrast, the addition of TGF-β1 attenuated all of the aforementioned effects of TNF-α. Our results demonstrate that TGF-β1 can decrease TNF-α-induced apoptosis in murine osteoblasts at least in part by attenuating TNF-α-induced caspase gene expression.
Citation Information
Chua, Chu C.; Chua, Balvin H.L.; Chen, Zhongyi; Landy, Cathy; and Hamdy, Ronald C.. 2002. TGF-β1 Inhibits Multiple Caspases Induced by TNF-α in Murine Osteoblastic MC3T3-E1 Cells. Biochimica et Biophysica Acta - Molecular Cell Research. Vol.1593(1). 1-8. https://doi.org/10.1016/S0167-4889(02)00257-4 PMID: 12431778 ISSN: 0167-4889