The influence of prostaglandin D2 on human mesenchymal stem cells

Objective: Periodontal regeneration starts with the proliferation and differentiation of progenitor cells and the formation of the extracellular matrix. Mesenchymal stem cells (hMSCs) are able to differentiate into cells of the periodontal complex and form periodontal tissue. Previous studies indicate, that prostaglandin D2 (PGD2) is a potent modulator of osteoblastic function and bone formation. The aim of this study was to observe the influence of PGD2 on proliferation and differentiation of hMSCs. Methods: hMSCs were cultivated with three different concentrations of PGD2 (0,1ng/ml; 0,5ng/ml; 1,0ng/ml). Cells were counted and the cumulative population doubling was calculated at 1, 2, and 4 weeks. Additionally hMSCs were stimulated with osteogenic supplements and PGD2. Following the osteogenic stimulation, the amount calcium deposition was determined and histologically assessed. The expression of osteogenic markers after 21 days was determined using RTQ-PCR. Statistical analysis was perfomed, using Games-Howell test at a level of significance of p<0.05. Results: Compared to the unstimulated control-group, the population-doubling of the 0,1ng/ml and the 1,0ng/ml PGD2 group decreased on day 21 and 28. The population doubling of the 0,5ng/ml PGD2 group was similar to that of the control-group. The amount of deposited calcium decreased in all PGD2 stimulated groups compared to the control group. The RNA-expression of alcaline phospatase (p<0,001) and collagen I (p<0,001) was significantly higher in the 0,5ng/ml concentration-group compared to the other PGD2 groups and the control group. Conclusion: The results indicate, that PGD2 has no effect on the proliferation rate but a strong effect on the regulation of osteogenic differentiation and bone formation at a concentration of 0,5ng/ml. Higher and lower concentrations of PGD2 inhibited the proliferation and the osteogenic differentiation of hMSC. Based on these observations it can be assumed, that the influence of PGD2 on hMSC follows a very fine regulated concentration-dependent system.