PMID- 12608905
OWN - NLM
STAT- MEDLINE
DCOM- 20030610
LR  - 20190906
IS  - 0022-3484 (Print)
IS  - 0022-3484 (Linking)
VI  - 38
IP  - 2
DP  - 2003 Apr
TI  - Basic fibroblast growth factor induces the expression of matrix 
      metalloproteinase-3 in human periodontal ligament cells through the MEK2 
      mitogen-activated protein kinase pathway.
PG  - 122-9
AB  - 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.
FAU - Shimazu, Atsushi
AU  - Shimazu A
AD  - Department of Preventive Dentistry, Faculty of Dentistry, Hiroshima University, 
      Hiroshima, Japan. atsushi@hiroshima-u.ac.jp
FAU - Morishita, Masayuki
AU  - Morishita M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Periodontal Res
JT  - Journal of periodontal research
JID - 0055107
RN  - 0 (Butadienes)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Flavonoids)
RN  - 0 (Nitriles)
RN  - 0 (Protein Synthesis Inhibitors)
RN  - 0 (Proteoglycans)
RN  - 0 (RNA, Messenger)
RN  - 0 (U 0126)
RN  - 103107-01-3 (Fibroblast Growth Factor 2)
RN  - 98600C0908 (Cycloheximide)
RN  - EC 2.7.1.- (MAP2K2 protein, human)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 2)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
RN  - VC2W18DGKR (Thymidine)
SB  - IM
MH  - Analysis of Variance
MH  - Butadienes/pharmacology
MH  - Calcium-Calmodulin-Dependent Protein Kinases/antagonists & inhibitors
MH  - Cell Culture Techniques
MH  - Cycloheximide/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Inhibitors/pharmacology
MH  - Fibroblast Growth Factor 2/administration & dosage/*pharmacology
MH  - Flavonoids/pharmacology
MH  - Gene Expression Regulation, Enzymologic/drug effects
MH  - Humans
MH  - MAP Kinase Kinase 2
MH  - Matrix Metalloproteinase 3/*drug effects/genetics
MH  - Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors/*pharmacology
MH  - Nitriles/pharmacology
MH  - Periodontal Ligament/*enzymology
MH  - Protein Synthesis Inhibitors/pharmacology
MH  - Protein-Tyrosine Kinases/antagonists & inhibitors/*pharmacology
MH  - Proteoglycans/antagonists & inhibitors/metabolism
MH  - RNA, Messenger/genetics
MH  - Thymidine/metabolism
MH  - Time Factors
MH  - Up-Regulation
EDAT- 2003/03/01 04:00
MHDA- 2003/06/11 05:00
CRDT- 2003/03/01 04:00
PHST- 2003/03/01 04:00 [pubmed]
PHST- 2003/06/11 05:00 [medline]
PHST- 2003/03/01 04:00 [entrez]
AID - 1o645 [pii]
AID - 10.1034/j.1600-0765.2003.01645.x [doi]
PST - ppublish
SO  - J Periodontal Res. 2003 Apr;38(2):122-9. doi: 10.1034/j.1600-0765.2003.01645.x.