GATA-3 transduces survival signals in osteoblasts through upregulation of bcl-x L gene expression

Abstract

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 stressinduced 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. ß

Improving effects of chitosan nanofiber scaffolds on osteoblast proliferation and maturation

“…16 Osteoblasts play a central role in mediating bone formation. 2,3 Our present data revealed that chitosan nanofiber scaffolds stimulated growth of mouse osteosarcoma UMR-106 cells and mouse calvarial osteoblasts. Also, we further demonstrated that chitosan nanofibers significantly improved the growth and proliferation of human osteoblasts.…”

“…Abbreviations: mrNa, messenger rNa; runx2, runt-related transcription factor 2; rT-Pcr, reverse transcription polymerase chain reaction. 3,9 An increase in ALP staining signals correspondingly indicates enhancement of osteoblast maturation. Such an effect of chitosan nanofibers on osteoblast development was also demonstrated by the Alizarin red-and von Kossa-staining assays.…”

“…1 Osteoblasts, which differentiate from stromal stem cells, were reported to play a central role in mediating bone formation. 2,3 Osteogenesis is the process of bone formation and consists of various consecutive stages, including osteoprogenitor proliferation, matrix maturation, and osteoblast mineralization. 4,5 In the beginning of bone turnover or fracture healing, stem cells and primitive osteoprogenitors proliferate and subsequently replace old and damaged osteoblasts.…”

Drynaria fortunei J. Sm. improves the bone mass of ovariectomized rats through osteocalcin-involved endochondral ossification

“…Oxidative stress is directly linked to estrogen decline and osteoporosis occurrence (Manolagas, 2010). Osteoblasts also mediate bone formation in bone remodeling but are easily insulted by oxidative stress (Ducy et al, 2000;Chen et al, 2010). Our previous studies reported that Kunze could protect osteoblasts from oxidative-and nitrosative stress-induced apoptotic injury (Liu et al, 2001;Huang et al, 2010).…”

Nanoparticles prepared from the water extract of Gusuibu (Drynaria fortunei J. Sm.) protects osteoblasts against insults and promotes cell maturation

“…10,11 A variety of biomolecules participate in regulating inflammation-induced osteoblast injury. [12][13][14] Reducing such stress-caused damage can promote osteoblast maturation and bone healing. Our previous studies showed that Gusuibu, a traditional Preparation of the water extract of gusuibu (Weg) and nanoparticles of the Weg (nWeg).…”