scholarly journals Regulation of Alternative Splicing of Fibronectin mRNA by Enamel Matrix Derivative in Human Gingival Fibroblasts.

Author(s):  
Ginko Osawa ◽  
Hiroshi Nakaya ◽  
Kyuichi Kamoi
2008 ◽  
Vol 87 (9) ◽  
pp. 850-855 ◽  
Author(s):  
E. Zeldich ◽  
R. Koren ◽  
M. Dard ◽  
C. Nemcovsky ◽  
M. Weinreb

We previously reported that EMD (Enamel Matrix Derivative) induces proliferation of human gingival fibroblasts via activation of Extracellular Regulated Kinase (ERK), and this study assessed the possible mediatory role of EGFR (Epidermal Growth Factor Receptor) in this effect. Treatment of gingival fibroblasts with EMD resulted in tyrosine phosphorylation of the EGFR, as assessed by immunoblotting and ELISA, while EMD-induced ERK activation and thymidine incorporation were markedly inhibited (~ 40–50%) by a specific EGFR tyrosine kinase inhibitor. Using appropriate inhibitors, we established that EMD-induced EGFR activation is largely due to shedding of HB-EGF (Heparin-binding EGF) from the cell membrane via a metalloproteinase-mediated process. Finally, the addition of PP1, a Src family inhibitor, abrogated both EGFR phosphorylation and ERK activation. Taken together, these results indicate that, at least in human gingival fibroblasts, EMD-induced ERK activation and proliferation are partially due to a Src-dependent, metalloproteinase-mediated transactivation of EGFR.


2007 ◽  
Vol 86 (1) ◽  
pp. 41-46 ◽  
Author(s):  
E. Zeldich ◽  
R. Koren ◽  
C. Nemcovsky ◽  
M. Weinreb

Emdogain®, a formulation of Enamel Matrix Proteins, is used clinically for periodontal regeneration to stimulate PDL (periodontal ligament), cementum, and bone formation. Its effects on gingival fibroblasts and tissue have not been thoroughly studied. Therefore, we investigated the mechanisms by which Emdogain affects the cell cycle of human gingival fibroblasts. Without serum, Emdogain (50 μg/mL) induced human gingival fibroblast entry into the S phase and DNA synthesis, but not completion of the cell cycle. With low serum concentrations (0.2–0.5%), Emdogain synergistically induced completion of the cell cycle, resulting in increased cell numbers. The mitogenic response to Emdogain depended on Extracellular Regulated Kinase (ERK) activation, which occurred in two waves, peaking after 15 min and 4 to 6 hrs, since it was abolished by U0126, a specific MAPK inhibitor. Inhibition of the second wave was sufficient to abrogate mitogenesis. This study characterized the mitogenic effect of Emdogain on primary human gingival fibroblasts, its cooperation with serum growth factors, and the key mediatory role of the ERK cascade.


2012 ◽  
Vol 2 (7) ◽  
pp. 323-325
Author(s):  
Dr. Ranjit Singh Uppal ◽  
◽  
Dr. Atamjit Singh Dr. Atamjit Singh ◽  
Dr. Rajbir Kaur ◽  
Dr. Navdeep Kaur Sodhi

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