Platelet-derived growth factor-BB stimulated cell migration mediated through p38 signal transduction pathway in periodontal cells.
BACKGROUND
Intracellular signaling pathways mediate specific responses to growth factors. The manipulation of these pathways ultimately may be used to control the clinical outcomes of periodontal regenerative therapy. The purpose of this study was to examine the role of the p38 signal transduction pathway in the responses of periodontal cells to platelet-derived growth factor-BB (PDGF).


METHODS
Primary cultures of human periodontal ligament cells (PDLs) and gingival fibroblasts (GFs) were used for all experiments. Cell numbers, 3H-thymidine incorporation, and Boyden chamber assays were used to characterize the effects of SB 203580 (SB), a specific inhibitor of the p38 signaling pathway, on cell proliferation and migration. An in vitro wound model also was used to assess the effects of SB. For the in vitro wound assay, triplicate wells were incubated for 1, 3, 5, and 7 days using 0.1% fetal bovine serum (FBS), 10% FBS +/- 10 microM SB, or 20 ng/ml PDGF +/- 10 microM SB. Digital histomorphometric analysis assessed cellular fill within the wound area.


RESULTS
SB specifically inhibited PDGF-induced migration in the Boyden chamber assays without affecting cell proliferation. The wound model data showed similar levels of wound fill for PDLs and GFs in 10% FBS. Relative to 10% FBS, PDLs stimulated with PDGF showed significantly (P < 0.01, analysis of variance) greater wound fill (74%) than GFs (12%). SB inhibited the PDGF-induced wound fill of PDLs and GFs by 64% and 57%, respectively. This inhibition was significant (P < 0.01, ANOVA) only for PDLs. The addition of SB to 10% FBS did not significantly affect the wound fill response of either cell type compared to 10% FBS alone.


CONCLUSIONS
These results demonstrate that periodontal cells possess distinct responses to PDGF that may be altered at the signal transduction level. The manipulation of these responses through the use of inhibitors to specific signaling pathways may enhance our control of periodontal regeneration in the future.
Department of Pathology, University of Texas Health Science Center, San Antonio, TX 78229-3900, USA.
Angel K
AK
Ray
Anne C
AC
Jones
David L
DL
Carnes
David L
DL
Cochran
James T
JT
Mellonig
Thomas W
TW
Oates
D000328:Adult; D000704:Analysis of Variance; D000077214:Becaplermin; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D015194:Diffusion Chambers, Culture; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects*; D005881:Gingiva / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000187:drug effects*; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D011725:Pyridines / Q000494:pharmacology; D011994:Recombinant Proteins; D015398:Signal Transduction / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases
D004791:Enzyme Inhibitors; D007093:Imidazoles; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011725:Pyridines; D011994:Recombinant Proteins; D000077214:Becaplermin; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580