TITLE:
The Role of Prostaglandin E2 on Osteoblast Proliferation Induced by Hydroxyapatite
AUTHORS:
Erwan Sugiatno, Endang Herminajeng, Wihaskoro Sosroseno
KEYWORDS:
Hydroxyapatite, Osteoblast, PGE2, Proliferation
JOURNAL NAME:
Journal of Biosciences and Medicines,
Vol.8 No.1,
January
8,
2020
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.