Abstract |
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.
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Authors | S S Kelpke, D Reiff, C W Prince, J A Thompson |
Journal | Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
(J Bone Miner Res)
Vol. 16
Issue 10
Pg. 1917-25
(Oct 2001)
ISSN: 0884-0431 [Print] United States |
PMID | 11585358
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Nitrates
- Sialoglycoproteins
- Spp1 protein, mouse
- Spp1 protein, rat
- Fibroblast Growth Factor 1
- Osteocalcin
- Osteopontin
- Peroxynitrous Acid
- Tyrosine
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Topics |
- Animals
- Cell Division
(drug effects)
- Cell Line
- Cell Survival
(drug effects)
- Fibroblast Growth Factor 1
(pharmacology)
- Mice
- Nitrates
(metabolism)
- Osteoblasts
(cytology, drug effects, metabolism)
- Osteocalcin
(genetics)
- Osteopontin
- Peroxynitrous Acid
(pharmacology)
- Rats
- Sialoglycoproteins
(biosynthesis, genetics)
- Signal Transduction
- Stem Cells
(cytology, drug effects, metabolism)
- Tyrosine
(metabolism)
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