JBM  Vol.8 No.1 , January 2020
The Role of Prostaglandin E2 on Osteoblast Proliferation Induced by Hydroxyapatite
Abstract: Objective: Prostaglandin E2 (PGE2) plays a crucial role in regulating bone cell differentiation and proliferation. The aim of the present study was to determine whether PGE2 may regulate osteoblast proliferation induced by hydroxyapatite. Materials and Methods: Osteoblasts (HOS cell line) pre-treated with cyclooxygenase (COX) inhibitors (indomethacin, aspirin and nimesulide) were then cultured. The cells were also pre-treated with or without nimesulide and then cultured with PGE2. The cell cultures were also treated with SQ22536 (adenylyl cyclase inhibitor) and added with Db-cAMP (cAMP analog), and/or PGE2. KT5720 [protein kinase A (PKA) inhibitor.], Db-cAMP and/or forskolin (adenylyl cyclase activator)-treated cultures were used to assess the role of PKA. The role of EP2 and/or EP4 was determined by using EP2 antagonist (PF-04418948) and EP4 antagonist (L-161,982) with PGE2. All cells were cultured with or without hydroxyapatite. The levels of PGE2 and cAMP were detected from the culture supernantants and the cell proliferation was assessed colorimetrically. Results: Nimesulide and indomethacin but not aspirin suppressed partially the cell proliferation but fully PGE2 production. PGE2 abrogated nimesulide-mediated suppression of cell proliferation. The cell proliferation was enhanced by low but suppressed by high concentration of PGE2. Moreover, the SQ22536-mediated suppression of cell proliferation was abolished by Db-cAMP but not PGE2. Conversely, PGE2, Db-cAMP or forskolin failed to eliminate KT5720-mediated suppression of cell proliferation. The effect of PGE2 on cell proliferation and cAMP levels was mediated predominantly via EP2 and to a lesser extent, EP4. The results of the controls for all experiments were significantly lower than hydroxyapatite-stimulated cell cultures. Conclusion: These results suggest thatPGE2, acting via a COX-2-, cAMP-PKA- and both EP2 and EP4-dependent pathway may partially regulate hydroxyapatite-induced human osteoblasts in an autocrine fashion.
Cite this paper: Sugiatno, E. , Herminajeng, E. and Sosroseno, W. (2020) The Role of Prostaglandin E2 on Osteoblast Proliferation Induced by Hydroxyapatite. Journal of Biosciences and Medicines, 8, 42-55. doi: 10.4236/jbm.2020.81006.

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