Document Detail

Fibroblast growth factor-2 stimulates directed migration of periodontal ligament cells via PI3K/AKT signaling and CD44/hyaluronan interaction.
MedLine Citation:
PMID:  20857427     Owner:  NLM     Status:  MEDLINE    
Fibroblast growth factor-2 (FGF-2) regulates a variety of functions of the periodontal ligament (PDL) cell, which is a key player during tissue regeneration following periodontal tissue breakdown by periodontal disease. In this study, we investigated the effects of FGF-2 on the cell migration and related signaling pathways of MPDL22, a mouse PDL cell clone. FGF-2 activated the migration of MPDL22 cells and phosphorylation of phosphatidylinositol 3-kinase (PI3K) and akt. The P13K inhibitors, Wortmannin and LY294002, suppressed both cell migration and akt activation in MPDL22, suggesting that the PI3K/akt pathway is involved in FGF-2-stimulated migration of MPDL22 cells. Moreover, in response to FGF-2, MPDL22 showed increased CD44 expression, avidity to hyaluronan (HA) partly via CD44, HA production and mRNA expression of HA synthase (Has)-1, 2, and 3. However, the distribution of HA molecular mass produced by MPDL22 was not altered by FGF-2 stimulation. Treatment of transwell membrane with HA facilitated the migration of MPDL22 cells and an anti-CD44 neutralizing antibody inhibited it. Interestingly, the expression of CD44 was colocalized with HA on the migrating cells when stimulated with FGF-2. Furthermore, an anti-CD44 antibody and small interfering RNA for CD44 significantly decreased the FGF-2-induced migration of MPDL22 cells. Taken together, PI3K/akt and CD44/HA signaling pathways are responsible for FGF-2-mediated cell motility of PDL cells, suggesting that FGF-2 accelerates periodontal regeneration by regulating the cellular functions including migration, proliferation and modulation of extracellular matrix production.
Yoshio Shimabukuro; Hiroaki Terashima; Masahide Takedachi; Kenichiro Maeda; Tomomi Nakamura; Keigo Sawada; Mariko Kobashi; Toshihito Awata; Hiroyuki Oohara; Takanobu Kawahara; Tomoaki Iwayama; Tomoko Hashikawa; Manabu Yanagita; Satoru Yamada; Shinya Murakami
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular physiology     Volume:  226     ISSN:  1097-4652     ISO Abbreviation:  J. Cell. Physiol.     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2010-12-30     Completed Date:  2011-01-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0050222     Medline TA:  J Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  809-21     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Wiley-Liss, Inc.
Division of Oral Biology and Disease Control, Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka, Japan.
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MeSH Terms
Antigens, CD44 / metabolism*
Cell Movement / drug effects*
Fibroblast Growth Factor 2 / pharmacology*
Gene Silencing / drug effects
Hyaluronic Acid / metabolism*
Mice, Inbred BALB C
Periodontal Ligament / cytology*,  drug effects,  enzymology
Phosphatidylinositol 3-Kinase / metabolism*
Phosphorylation / drug effects
Protein Binding / drug effects
Proto-Oncogene Proteins c-akt / metabolism*
Pseudopodia / drug effects,  metabolism
RNA, Small Interfering / metabolism
Signal Transduction / drug effects
Up-Regulation / drug effects
Reg. No./Substance:
0/Antigens, CD44; 0/RNA, Small Interfering; 103107-01-3/Fibroblast Growth Factor 2; 9004-61-9/Hyaluronic Acid; EC 3-Kinase; EC Proteins c-akt

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