| Involvement of ligand occupancy in Insulin-like growth factor-I (IGF-I) induced cell growth in osteoblast like MC3T3-E1 cells. | |
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MedLine Citation:
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PMID: 18057550 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Growth factors and matrix proteins regulate the proliferation and differentiation of osteoblasts. The insulin-like growth factor (IGF) system comprises IGF-I, IGF-II, and six high-affinity IGF-binding proteins (IGFBPs). IGFs stimulate cell growth in many types of tissue; IGF-binding proteins regulate cellular actions and can affect cell growth. IGF-I is involved in differentiation, proliferation, and matrix formation in osteoblasts; IGFBP-5 is associated with the extracellular matrix (ECM) and can potentiate the actions of IGF-I. We investigated the effect of ECM proteins on the responses of MC3T3-E1 osteoblast cells to IGF-I and IGFBP-5. In addition, because extracellular signal-regulated kinases 1 and 2 (Erk 1/2) affect cell growth, we evaluated the effects of IGFBP-5 on Erk 1/2 phosphorylation in MC3T3-E1 cells. IGF-I caused an increase in IGFBP-5 expression in cultured MC3T3-E1 cells, and IGF-I plus IGFBP-5 significantly increased cell growth. Likewise, the addition of IGF-I and IGFBP-5 to cultured MC3T3-E1 cells increased the synthesis of the ECM proteins osteopontin (OPN) and thrombospondin-1 (TSP-1), which can bind to alphaVbeta3 integrin receptors on the cell surface. By contrast, the addition of an antibody against ECM proteins inhibited the effects of OPN and TSP-1 on IGFBP-5 expression. The stimulatory effect of IGFBP-5 was mediated via Erk 1/2 activation. These data suggest that IGFBP-5 regulates Erk 1/2 phosphorylation in cultured MC3T3-E1 cells via ECM proteins that may ultimately stimulate the growth of osteoblasts. We determined whether occupation of the alphaVbeta3 integrin receptor affects IGF-I receptor (IGF-IR)-mediated signaling and function in MC3T3-E1 osteoblast cells. Occupation of the alphaVbeta3 integrin receptor with ECM proteins induced IGF-I-stimulated IGF-IR phosphorylation. Conversely, in the presence of the alphaVbeta3-specific disintegrin echistatin, IGF-I-stimulated IGF-IR activation was inhibited. IGF-I-stimulated IGF-IR phosphorylation was accompanied by IRS-1 phosphorylation and MAPK activation. However, these effects were attenuated by echistatin. Thus, occupancy of the alphaVbeta3 disintegrin receptor modulates IGF-I-induced IGF-IR activation and IGF-IR-mediated function in MC 3T3-E1 osteoblasts. |
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Authors:
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Seok-Kwun Kim; Ji-Young Kwon; Taek-Jeong Nam |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: BioFactors (Oxford, England) Volume: 29 ISSN: 0951-6433 ISO Abbreviation: Biofactors Publication Date: 2007 |
Date Detail:
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Created Date: 2007-12-06 Completed Date: 2008-04-14 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 8807441 Medline TA: Biofactors Country: Netherlands |
Other Details:
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Languages: eng Pagination: 187-202 Citation Subset: IM |
Affiliation:
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Department of Plastic and Reconstructive Surgery, College of Medicine, Dong-A University, Seo-Gu, Busan, South Korea. sgkim1@daunet.donga.ac.kr |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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3T3 Cells Animals Binding Sites / drug effects Blotting, Northern Blotting, Western Cell Line Cell Movement / drug effects Cell Proliferation / drug effects* Cells, Cultured Extracellular Matrix / drug effects Extracellular Signal-Regulated MAP Kinases / drug effects, metabolism Humans Insulin-Like Growth Factor Binding Protein 5 / biosynthesis, pharmacology* Insulin-Like Growth Factor I / pharmacology* Integrin alphaVbeta3 / antagonists & inhibitors, drug effects, metabolism Ligands Mice Osteoblasts / drug effects*, metabolism Osteopontin / metabolism Peptides / pharmacology Phosphorylation / drug effects Protein Binding / drug effects Signal Transduction / drug effects Thrombospondin 1 / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Insulin-Like Growth Factor Binding Protein 5; 0/Integrin alphaVbeta3; 0/Ligands; 0/Peptides; 0/Thrombospondin 1; 106441-73-0/Osteopontin; 118337-11-4/echistatin; 67763-96-6/Insulin-Like Growth Factor I; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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