Acidic fibroblast growth factor signaling inhibits peroxynitrite-induced death of osteoblasts and osteoblast precursors.
After trauma injury to the musculoskeletal system, conditions such as ischemia and inflammation involve excess production of superoxide (O2*), 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.
Kelpke
S S
SS
Department of Surgery, The University of Alabama at Birmingham, USA.
Reiff
D
D
Prince
C W
CW
Thompson
J A
JA
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology*; D051379:Mice; D009566:Nitrates / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015675:Osteocalcin / Q000235:genetics; D053495:Osteopontin; D030421:Peroxynitrous Acid / Q000494:pharmacology*; D051381:Rats; D012795:Sialoglycoproteins / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D009566:Nitrates; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; C506897:Spp1 protein, rat; D016220:Fibroblast Growth Factor 1; D015675:Osteocalcin; D053495:Osteopontin; D030421:Peroxynitrous Acid; D014443:Tyrosine