Prostaglandin F(2alpha) 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) F(2alpha) in the differentiation of mouse ST2 mesenchymal stem cells (MSC) into adipocytes and osteoblasts. PGF(2alpha) was not produced in the undifferentiated ST2 MSC, but its highest level of production was detected at 3h after the initiation of adipogenesis and then quickly decreased. On the contrary, apparent PGF(2alpha) production was not detected during the osteoblastogenesis of ST2 MSC. The PGF(2alpha) production pattern during adipogenesis well resembled the expression profiles of aldo-keto reductase (AKR) 1B3, which acted as the PGF(2alpha) 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 PGF(2alpha) 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 PGF(2alpha) suppressed the early phase of adipogenesis through FP receptors, but did not affect osteoblastogenesis in ST2 MSC. Therefore, PGF(2alpha) suppressed the progression of early phase adipogenesis after determination of the cell fate that causes MSC to differentiate into adipocytes.
Fujimori
Ko
K
Laboratory of Biodefense and Regulation, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan. fujimori@gly.oups.ac.jp
Ueno
Toshiyuki
T
Amano
Fumio
F
D050156:Adipogenesis / Q000187:drug effects*; D000429:Alcohol Oxidoreductases / Q000235:genetics / Q000378:metabolism; D000449:Aldehyde Reductase; D000074408:Aldo-Keto Reductases; D000818:Animals; D002454:Cell Differentiation; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015237:Dinoprost / Q000494:pharmacology*; D006911:Hydroxyprostaglandin Dehydrogenases / Q000235:genetics / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*
D015237:Dinoprost; D000429:Alcohol Oxidoreductases; D000074408:Aldo-Keto Reductases; D006911:Hydroxyprostaglandin Dehydrogenases; C031051:prostaglandin-F synthase; D000449:Aldehyde Reductase; C000614209:AKR7A5 protein, mouse; D051546:Cyclooxygenase 2