title: Differential effects of prostaglandin E(2) and enamel matrix derivative on the proliferation of human gingival and dermal fibroblasts and gingival keratinocytes.
abstract: OBJECTIVE
  Elevated levels of prostaglandins contribute to periodontal destruction but can impair gingival healing by affecting local fibroblasts. Enamel matrix derivative (EMD) has beneficial effects on supporting and gingival tissues. We showed that prostaglandin E(2) (PGE(2) ) inhibits the proliferation of human gingival fibroblasts (hGFs) and that EMD stimulates it. Prostaglandins and EMD may also affect skin healing by targeting dermal fibroblasts (DFs). Thus, we compared the effects of these two agents on the proliferation of hGFs, human gingival keratinocytes (hGKs) and hDFs.
  
  
  METHODS
  Cells from healthy human gingiva or skin were treated with PGE(2) and/or EMD, and proliferation was assessed by measuring cell number and DNA synthesis.
  
  
  RESULTS
  In hGFs, PGE(2) (1 μm) inhibited proliferation while EMD stimulated it. When present together, EMD abolished the PGE(2) -induced inhibition. Serum increased (by a factor of 10) the amount of phosphorylated extracellular signal-regulated kinase (p-ERK), PGE(2) reduced it (by 70-80%) and EMD restored it when present with PGE(2). Prostaglandin E(2) stimulated cAMP production in hGFs while serum or EMD did not. Enamel matrix derivative stimulated hDF proliferation, but the inhibitory effect of PGE(2) was milder than with hGFs. When present together, EMD abolished the PGE(2) -induced inhibition. Enamel matrix derivative inhibited the proliferation of primary hGKs, but PGE(2) had no effect. Finally, we found that hDFs contained about five times less prostaglandin EP(2) receptor mRNA than hGFs, while hGKs contained none.
  
  
  CONCLUSIONS
  Prostaglandin E(2) inhibits and EMD stimulates hGF proliferation via distinct pathways. The different sensitivities of hDFs and hGKs to PGE(2) can be explained by the levels of EP(2) expression.
authors.affiliation: Department of Oral Biology, the Maurice and Gabriela Goldschleger School of Dental Medicine, Tel-Aviv University, Tel-Aviv, Israel. © 2010 John Wiley & Sons A/S
authors.forename: E
authors.initials: E
authors.lastname: Weinberg
authors.forename: M
authors.initials: M
authors.lastname: Topaz
authors.forename: M
authors.initials: M
authors.lastname: Dard
authors.forename: P
authors.initials: P
authors.lastname: Lyngstadaas
authors.forename: C
authors.initials: C
authors.lastname: Nemcovsky
authors.forename: M
authors.initials: M
authors.lastname: Weinreb
mesh_terms: D000704:Analysis of Variance; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D003746:Dental Enamel Proteins / Q000494:pharmacology*; D020405:Dermis / Q000166:cytology / Q000187:drug effects*; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects*; D005881:Gingiva / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018709:Statistics, Nonparametric
chemical_list: D003746:Dental Enamel Proteins; C109069:enamel matrix proteins; D000242:Cyclic AMP; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases; D015232:Dinoprostone