Possible involvement of extracellular signal-regulated kinases 1/2 in mitogenic response of periodontal ligament cells to enamel matrix derivative.
The efficacy of enamel matrix derivative (EMD) as an adjunct to periodontal regenerative therapy has been demonstrated in recent clinical studies, however, little is known about its molecular mechanism (s). We examined the mitogenic response of cultured periodontal ligament (PDL) cells to EMD and characterized associated changes in proliferation-related intracellular signaling molecules, including mitogen-activated protein kinases (MAPK) and Akt kinases/protein kinase B (Akt/PKB) kinases. The DNA synthesis of PDL cells increased following treatment with EMD at concentrations higher than 1 microg ml(-1). This mitogenic response to EMD was associated with the selective activation of extracellular signal-regulated kinase (ERK) 1/2. No other MAPKs, or Akt/PKB kinases, responded to EMD stimulation. The EMD induction of DNA synthesis and activation of ERK 1/2 were diminished by pretreatment with suramin, an inhibitor of receptor tyrosine kinases (RTK). The signaling pathway induced by EMD from RTK to ERK 1/2 was similar to that activated by epidermal growth factor (EGF), although the specific binding of 125I-EGF to PDL cells was not affected by pretreatment or concomitant treatment with EMD. These findings suggest that EMD elicits its mitogenic signal through an EMD-specific RTK towards ERK 1/2.
Matsuda
Naoki
N
Radioisotope Center, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan. nuric@net.nagasaki-u.ac.jp
Horikawa
Miwa
M
Watanabe
Masami
M
Kitagawa
Syoji
S
Kudo
Yasusei
Y
Takata
Takashi
T
D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects; D003746:Dental Enamel Proteins / Q000494:pharmacology*; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008934:Mitogens / Q000494:pharmacology*; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D010766:Phosphorylation; D011485:Protein Binding; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism
D003746:Dental Enamel Proteins; D008934:Mitogens; C109069:enamel matrix proteins; D004815:Epidermal Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases