Differential effects of prostaglandin E₂ and enamel matrix derivative on the proliferation of human gingival and dermal fibroblasts and gingival keratinocytes

Background and 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 E₂ (PGE₂) 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.Material and Methods: Cells from healthy human gingiva or skin were treated with PGE₂ and/or EMD, and proliferation was assessed by measuring cell number and DNA synthesis. Results: In hGFs, PGE₂ (1 μm) inhibited proliferation while EMD stimulated it. When present together, EMD abolished the PGE₂ induced inhibition. Serum increased (by a factor of 10) the amount of phosphorylated extracellular signal regulated kinase (p ERK), PGE₂ reduced it (by 70-80%) and EMD restored it when present with PGE₂. Prostaglandin E₂ stimulated cAMP production in hGFs while serum or EMD did not. Enamel matrix derivative stimulated hDF proliferation, but the inhibitory effect of PGE₂ was milder than with hGFs. When present together, EMD abolished the PGE₂ induced inhibition. Enamel matrix derivative inhibited the proliferation of primary hGKs, but PGE₂ had no effect. Finally, we found that hDFs contained about five times less prostaglandin EP₂ receptor mRNA than hGFs, while hGKs contained none.Conclusion: Prostaglandin E₂ inhibits and EMD stimulates hGF proliferation via distinct pathways. The different sensitivities of hDFs and hGKs to PGE₂ can be explained by the levels of EP₂ expression.