Basic Fibroblast Growth Factor Induces The Expression of Matrix Metalloproteinase-3 in Human Periodontal Ligament Cells Through the MEK2 Mitogen-Activated Protein Kinase Pathway
Use this link to cite this item : https://ir.lib.hiroshima-u.ac.jp/00021547
ID | 21547 |
file | |
creator |
Morishita, Masayuki
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subject | periodontal ligament (PDL)
basic fibroblast growth factor (bFGF, FGF-2)
matrix metalloproteinase (MMP) -3
mitogen-activated protein (MAP) kinase
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NDC |
Medical sciences
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abstract | Basic fibroblast growth factor (bFGF, FGF-2) is one of the potent mitogens for periodontal ligament (PDL) cells. However, the role of bFGF on the matrix metalloproteinase-3 (MMP-3) expression in PDL cells is unknown. In this study, the effect of bFGF on MMP-3 expression in PDL cells and the mechanism of this process were examined. Human PDL cells were exposed to bFGF at various concentrations (0.01–10 ng/ml) in monolayer cultures. bFGF increased [3H]thymidine incorporation and suppressed proteoglycan synthesis concentration-dependently. However, similar concentration ranges of bFGF increased the release of the cell-associated proteoglycans into the medium. Furthermore, bFGF increased MMP-3 mRNA levels concentration-dependently as examined by reverse transcription-polymerase chain reaction (RT-PCR). Induction of MMP-3 after the stimulation with bFGF was observed as early as 12 h with maximal at 24 h. Thereafter, the MMP-3 mRNA level gradually decreased until 72 h. Cycloheximide blocked the induction of MMP-3 by bFGF, indicating the requirement of de novo protein synthesis for this stimulation. Furthermore, MMP-3 expression induced by bFGF was abrogated by U0126, a specific inhibitor of MEK1/2 and ERK1/2 in mitogen-activated protein (MAP) kinase pathway, not by PD98059, a specific inhibitor of MEK1. In addition, bFGF up-regulated the phosphorylated ERK1/2 in 5 min with the maximal at 20 min as examined by Western blotting, and U0126 inhibited the ERK1/2 phosphorylation induced by bFGF. These findings suggest that bFGF induces MMP-3 expression in PDL cells through the activation of the MEK2 in MAP kinase pathway. bFGF stimulation on MMP-3 synthesis may be involved in the control of the cell-associated proteoglycans in PDL cells during periodontal regeneration and degradation.
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journal title |
Journal of Periodontal Research
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volume | Volume 38
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issue | Issue 2
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start page | 122
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end page | 129
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date of issued | 2003
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publisher | Blackwell
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issn | 0022-3484
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ncid | |
publisher doi | |
language |
eng
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nii type |
Journal Article
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HU type |
Journal Articles
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DCMI type | text
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format | application/pdf
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text version | author
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rights | Copyright (c) 2003 Blackwell Publishing. The definitive version is available at www.blackwell-synergy.com
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relation url | |
department |
Graduate School of Biomedical Science
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