Document Detail


Fibroblast growth factor (FGF)-2 directly stimulates mature osteoclast function through activation of FGF receptor 1 and p42/p44 MAP kinase.
MedLine Citation:
PMID:  10896947     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We previously reported that fibroblast growth factor-2 (FGF-2) acts not only on osteoblasts to stimulate osteoclastic bone resorption indirectly but also on mature osteoclasts directly. In this study, we investigated the mechanism of this direct action of FGF-2 on mature osteoclasts using mouse and rabbit osteoclast culture systems. FGF-2 stimulated pit formation resorbed by isolated rabbit osteoclasts moderately from low concentrations (>/=10(-12) m), whereas at high concentrations (>/=10(-9) m) it showed stimulation on pit formation resorbed by unfractionated bone cells very potently. FGF-2 (>/=10(-12) m) also increased cathepsin K and MMP-9 mRNA levels in mouse and rabbit osteoclasts. Among FGF receptors (FGFR1 to 4) only FGFR1 was detected on isolated mouse osteoclasts, whereas all FGFRs were identified on mouse osteoblasts. FGF-2 (>/=10(-12) m) up-regulated the phosphorylation of cellular proteins, including p42/p44 mitogen-activated protein (MAP) kinase, and increased the kinase activity of immunoprecipitated FGFR1 in mouse osteoclasts. The stimulation of FGF-2 on mouse and rabbit osteoclast functions was abrogated by PD-98059, a specific inhibitor of p42/p44 MAP kinase. These results strongly suggest that FGF-2 acts directly on mature osteoclasts through activation of FGFR1 and p42/p44 MAP kinase, causing the stimulation of bone resorption at physiological or pathological concentrations.
Authors:
D Chikazu; Y Hakeda; N Ogata; K Nemoto; A Itabashi; T Takato; M Kumegawa; K Nakamura; H Kawaguchi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  275     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2000 Oct 
Date Detail:
Created Date:  2000-10-23     Completed Date:  2000-11-13     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  31444-50     Citation Subset:  IM    
Affiliation:
Departments of Orthopaedic Surgery and Oral and Maxillofacial Surgery, Graduate School of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo, Tokyo 113-8655, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blotting, Northern
Bone and Bones / metabolism
Cathepsin K
Cathepsins / biosynthesis
Cell Survival
Cells, Cultured
Cyclooxygenase Inhibitors / pharmacology
Dose-Response Relationship, Drug
Enzyme Inhibitors / pharmacology
Fibroblast Growth Factor 2 / metabolism*
Flavonoids / pharmacology
Immunoblotting
Kinetics
Male
Matrix Metalloproteinase 2 / biosynthesis
Mice
Mitogen-Activated Protein Kinase 1 / metabolism*
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinases / metabolism
Nitrobenzenes / pharmacology
Osteoblasts / metabolism
Osteoclasts / metabolism*
Phosphorylation
Precipitin Tests
Protein-Tyrosine Kinases*
RNA, Messenger / metabolism
Rabbits
Receptor Protein-Tyrosine Kinases / metabolism*
Receptor, Fibroblast Growth Factor, Type 1
Receptor, Fibroblast Growth Factor, Type 2
Receptor, Fibroblast Growth Factor, Type 3
Receptor, Fibroblast Growth Factor, Type 4
Receptors, Fibroblast Growth Factor / metabolism*
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
Sulfonamides / pharmacology
Time Factors
Tyrosine / metabolism
Up-Regulation
Chemical
Reg. No./Substance:
0/2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; 0/Cyclooxygenase Inhibitors; 0/Enzyme Inhibitors; 0/Flavonoids; 0/Nitrobenzenes; 0/RNA, Messenger; 0/Receptors, Fibroblast Growth Factor; 0/Sulfonamides; 103107-01-3/Fibroblast Growth Factor 2; 123653-11-2/N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; 55520-40-6/Tyrosine; EC 2.7.10.1/Fgfr1 protein, mouse; EC 2.7.10.1/Fgfr2 protein, mouse; EC 2.7.10.1/Fgfr3 protein, mouse; EC 2.7.10.1/Fgfr4 protein, mouse; EC 2.7.10.1/Protein-Tyrosine Kinases; EC 2.7.10.1/Receptor Protein-Tyrosine Kinases; EC 2.7.10.1/Receptor, Fibroblast Growth Factor, Type 1; EC 2.7.10.1/Receptor, Fibroblast Growth Factor, Type 2; EC 2.7.10.1/Receptor, Fibroblast Growth Factor, Type 3; EC 2.7.10.1/Receptor, Fibroblast Growth Factor, Type 4; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3; EC 2.7.11.24/Mitogen-Activated Protein Kinases; EC 3.4.-/Cathepsins; EC 3.4.22.38/Cathepsin K; EC 3.4.22.38/Ctsk protein, mouse; EC 3.4.24.24/Matrix Metalloproteinase 2

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