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GATA‐3 transduces survival signals in osteoblasts through upregulation of bcl‐x L gene expression
Author(s) -
Chen RueiMing,
Lin YiLing,
Chou ChihWei
Publication year - 2010
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.121
Subject(s) - downregulation and upregulation , gene expression , microbiology and biotechnology , gene , regulation of gene expression , chemistry , biology , biochemistry
GATA‐3, a transcription factor, participates in regulating cell development, proliferation, and death. This study was aimed at evaluating the roles of GATA‐3 in protecting osteoblasts against oxidative stress–induced apoptotic insults and their possible mechanisms. Pretreatment with nitric oxide (NO) for 24 hours protected osteoblasts, prepared from neonatal rat calvaria, against oxidative stress–induced apoptotic insults. Such protection involved enhancement of Bcl‐X L messenger (m)RNA and protein syntheses and the translocation of this antiapoptotic protein from the cytoplasm to mitochondria. GATA‐3 was detected in rat osteoblasts, and GATA‐3‐specific DNA‐binding elements exist in the promoter region of the bcl‐x L gene. NO preconditioning attenuated oxidative stress–caused suppression of GATA‐3 mRNA and protein synthesis and the translocation of this transcription factor from the cytoplasm to nuclei. Application of GATA‐3 small interfering (si)RNA into osteoblasts decreased the levels of this transcription factor and simultaneously inhibited Bcl‐X L mRNA synthesis. Pretreatment with NO lowered the oxidative stress–caused alteration in the binding of GATA‐3 to its specific DNA motifs. Oxidative stress–inhibited Runx2 mRNA expression, but NO preconditioning decreased such inhibition. NO pretreatment time‐dependently enhanced the association of GATA‐3 with Runx2. Knocking down the translation of GATA‐3 using RNA interference significantly decreased the protection of NO preconditioning against oxidative stress–induced alterations of cell morphologies, DNA fragmentation, and cell apoptosis. In comparison, overexpression of GATA‐3 could promote NO preconditioning–involved Bcl‐X L expression and cell survival. Therefore, this study shows that GATA‐3 plays critical roles in mediating survival signals in osteoblasts, possibly through upregulating bcl‐x L gene expression. © 2010 American Society for Bone and Mineral Research.