Prostaglandin F2α suppresses early phase of adipogenesis, but is not associated with osteoblastogenesis in mouse mesenchymal stem cells

In this study, we investigated the roles of prostaglandin (PG) F2α in the differentiation of mouse ST2 mesenchymal stem cells (MSC) into adipocytes and osteoblasts. PGF2α was not produced in the undifferentiated ST2 MSC, but its highest level of production was detected at 3 h after the initiation of adipogenesis and then quickly decreased. On the contrary, apparent PGF2α production was not detected during the osteoblastogenesis of ST2 MSC. The PGF2α production pattern during adipogenesis well resembled the expression profiles of aldo-keto reductase (AKR) 1B3, which acted as the PGF2α synthase, and cyclooxygenase-2 genes; but the pattern showed a slight delay compared with these profiles. The siRNA for AKR1B3, but not that for AKR1B8 or 1B10, decreased PGF2α production and enhanced the expression of adipogenic genes, but did not affect the mRNA levels of osteoblastogenic genes, during the adipogenesis of ST2 MSC. The FP receptor was expressed during adipogenesis of ST2 MSC, and its agonist or antagonist suppressed or enhanced, respectively, the lipid accumulation and the adipogenic gene expression; but this receptor was not associated with the osteoblastogenesis. These results indicate that AKR1B3-mediated PGF2α suppressed the early phase of adipogenesis through FP receptors, but did not affect osteoblastogenesis in ST2 MSC. Therefore, PGF2α suppressed the progression of early phase adipogenesis after determination of the cell fate that causes MSC to differentiate into adipocytes.

Research highlights▶ PGF2α is not involved in the regulation of osteoblastogenesis in mesenchymal stem cells. ▶ PGF2α is not associated to the determination of cell fate of differentiation to adipocytes from mesenchymal stem cells. ▶ AKR1B3-mediated PGF2α suppressed the early phase of adipogenesis through FP receptors.