Basic fibroblast growth factor stimulates fibronectin expression through phospholipase C γ, protein kinase C α, c‐Src, NF‐κB, and p300 pathway in osteoblasts

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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 phosphatidylinositol phospholipase inhibitor (U73122), protein kinase C inhibitor (GF109203X), Src inhibitor (PP2), NF‐κB inhibitor (PDTC), IκBα phosphorylation inhibitor (Bay 117082), or IκB protease inhibitor (TPCK). bFGF‐induced increase of Fn‐luciferase activity was antagonized by cells transfected with Fn construct without NF‐κB regulatory site. Stimulation of osteoblasts with bFGF activated IκB kinase α/β (IKK α/β) and increased IκBα phosphorylation, IκBα degradation, p65 and p50 translocation from the cytosol to the nucleus, the formation of an NF‐κB‐specific DNA‐protein complex and κB‐luciferase activity. bFGF‐mediated an increase of IKKα/β activity and DNA‐binding activity was inhibited by U73122, GF109203X, or PP2. The binding of p65 to the NF‐κB element, as well as the recruitment of p300 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 PLCγ2, PKCα, c‐Src, IKKα, or IKKβ. Our results suggest that bFGF increased Fn expression in rat osteoblasts via the FGFR2/PLCγ2/PKCα/c‐Src/NF‐κB signaling pathway. J. Cell. Physiol. 211: 45–55, 2007.