Effects of prostaglandin E2 and D2 on cell proliferation and osteogenic capacity of human mesenchymal stem cells

Abstract

The manifestation of periodontitis-related inflammatory reaction is inevitably bound to the production of prostaglandins E₂ and D₂ which have been suggested to mediate osteoclastic and osteogenic effects within the affected tissue. We demonstrated the presence of PGE₂ and PGD₂ receptors on hMSCs on RNA level and with immunofluorescence. For each Prostaglandin, three concentrations were studied: 0.1; 0.5 or 1.0 µg/ml. A lower expression of EP1 and EP4 (PGE₂ receptors 1 and 4) after stimulation with PGE₂ was shown, thus a tendency to compromise osteogenic differentiation and metabolism. PGE₂ induced a higher growth-rate during the first week, while a continuous inflammatory challenge determined a decrease of the proliferation of hMSCs. PGD₂ inhibited cell growth irrespective of the duration of the stimulation. PGE₂ and PGD₂ have also negative effects on calcium deposition osteogenic, thus on differentiation of hMSCs. PGE₂ and PGD₂ seem to induce bone resorption also having indirectly a negative impact on the osteogenic differentiation of hMSCs. Thus, inhibitors of PGE₂ and PGD₂ can be used as adjunct to mechanical periodontal treatment.

Keywords: Bone loss; Bone remodeling; Cell differentiation; Inflammation; Osteogenesis; Periodontitis.