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Acidic Fibroblast Growth Factor Signaling Inhibits Peroxynitrite‐Induced Death of Osteoblasts and Osteoblast Precursors
Author(s) -
Kelpke S. S.,
Reiff D.,
Prince C. W.,
Thompson J. A.
Publication year - 2001
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 - 10.1359/jbmr.2001.16.10.1917
Subject(s) - osteopontin , peroxynitrite , osteoblast , tyrosine phosphorylation , fibroblast growth factor , osteocalcin , microbiology and biotechnology , chemistry , programmed cell death , fibroblast , basic fibroblast growth factor , nitrotyrosine , nitric oxide , signal transduction , apoptosis , growth factor , endocrinology , biochemistry , biology , nitric oxide synthase , superoxide , alkaline phosphatase , in vitro , receptor , enzyme
After trauma injury to the musculoskeletal system, conditions such as ischemia and inflammation involve excess production of superoxide (), nitric oxide ( · NO), and their reaction product, peroxynitrite (ONOO − ). Exposure of murine osteoblasts and rat‐derived primary osteoblast precursors to ONOO − resulted in a dose‐ and time‐dependent delayed cell death that was more characteristic of apoptosis than necrosis. Exposure of both cell populations to ONOO − immediately enhanced phosphorylation and nitration of tyrosine residues within several polypeptides. Treatment of osteoblasts and osteoblast precursors with exogenous acidic fibroblast growth factor (FGF‐1) enhanced cellular growth, increased endogenous levels of tyrosine phosphorylation, and significantly induced expression of both osteopontin and osteocalcin messenger RNA (mRNA) as well as osteopontin protein. Pretreatment of both cell populations with exogenous FGF‐1 prevented ONOO − ‐mediated death. Cell signaling induced by FGF‐1 pretreatment had no major effect of total levels of tyrosine nitration after ONOO − treatment. Collectively, these in vitro efforts show that FGF‐1 signaling renders osteoblasts and osteoblast precursors resistant to the cytotoxic effects of ONOO − . Consequently, results presented here predict the therapeutic use of this growth factor for promoting the progression of bone repair mechanisms after fracture trauma.