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  4. Basic Fibroblast Growth Factor Stimulates Fibronectin Expression through Phospholipase C Alpha, Protein Kinase C Alpha, C-Src, Nf-Kappa B, and P300 Pathway in Osteoblasts
 
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Basic Fibroblast Growth Factor Stimulates Fibronectin Expression through Phospholipase C Alpha, Protein Kinase C Alpha, C-Src, Nf-Kappa B, and P300 Pathway in Osteoblasts

Resource
JOURNAL OF CELLULAR PHYSIOLOGY v.211 n.1 pp.45-55
Journal
JOURNAL OF CELLULAR PHYSIOLOGY
Journal Volume
v.211
Journal Issue
n.1
Pages
45-55
Date Issued
2007
Date
2007
Author(s)
TANG, CHIH-HSIN
YANG, RONG-SEN
CHEN, YUH-FUNG
FU, WEN-MEI
URI
http://ntur.lib.ntu.edu.tw//handle/246246/92441
Abstract
Fibronectin (Fn) is involved in early stages of bone formation and basic fibroblast growth factor (bFGF) is an important factor regulating osteogenesis. bFGF increased Fn expression, which was attenuated by phosphaticylinositol phospholipase inhibitor (U73122), protein kinase C inhibitor (GF109203X), Src inhibitor (PP2), NF-kappa B inhibitor ( PDTC), I kappa B alpha phosphorylation inhibitor (Bay 1 17082), or I kappa B protease inhibitor (TPCK). bFGF-induced increase of Fn-luciferase activity was antagonized by cells transfected with Fn construct without NF-kappa B regulatory site. Stimulation of osteoblasts with bFGF activated I kappa B kinase alpha/beta (IKK alpha/beta) and increased I kappa B alpha phosphorylation, I kappa B alpha degradation, p65 and p50 translocation from the cytosol to the nucleus, the formation of an NF-kappa B-specific DNA-protein complex and kappa B-luciferase activity. bFGF-mediated an increase of IKK alpha/beta activity and DNA-binding activity was inhibited by U73122, GF109203X, or PP2. The binding of p65 to the NF-kappa B element, as well as the recruitment of p 300 and the enhancement of p50 acetylation on the Fn promoter was enhanced by bFGF. Overexpression of constitutively active FGF receptor 2 (FGFR2) increased Fn- luciferase activity, which was inhibited by co-transfection with dominant negative ( DN) mutants of PLC-gamma 2, PKC alpha, c-Src, IKK gamma, or IKK beta. Our results suggest that bFGF increased Fn expression in rat osteoblasts via the FGFR2/PLC gamma 2/PKC alpha/c-Src/NF-kappa B signaling pathway.
Subjects
CULTURED RAT OSTEOBLASTS
FRACTURE REPAIR
ACTIVATION
RECEPTOR
FIBRILLOGENESIS
INTEGRIN

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