The EP4-ERK-dependent pathway stimulates osteo-adipogenic progenitor proliferation resulting in increased adipogenesis in fetal rat calvaria cell cultures
Aubin, Jane E.
Selective EP agonists
Rat calvaria cells
We previously reported that fetal rat calvaria (RC) cells are osteo-adipogenic bipotential and that PGE2 receptors EP2 and EP4 are involved in bone nodule formation via both common and distinct MAPK pathways in RC cell cultures. Because PGE2 participates in multiple biological processes including adipogenesis, it is of interest to determine the additional role(s) of PGE2 in RC cells. PGE2 increased the number of adipocyte colonies when RC cells were treated during proliferation but not other development stages. Of four EP agonists tested, the EP4 agonist ONO-AE1-437 (EP4A) was the most effective in promoting adipogenesis. Concomitantly, EP4A increased the number of cells with BrdU labeling and gene expression of CCAAT/enhancer binding protein (C/EBP)δ and c-fos but not peroxisome proliferator-activated receptor γ2 and C/EBPα. Amongst MAPK inhibitors, U0126, an inhibitor of MEK1/2, abrogated the EP4A-dependent effects. Our results suggest that the PGE2–EP4-ERK pathway increases the number of osteo-adipogenic bipotential progenitor cells, with a resultant increase in adipogenesis in RC cell cultures.
This work was supported in part by grants from the Ministry of Education, Science, Sports and Culture of Japan (13771074 to YY)and Ono Pharmaceutical Co. (to YY), and the Canadian Institutes of Health Research (CIHR; FRN 83704 to JEA).
Prostaglandins & Other Lipid Mediators
|date of issued||
© 2012. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
This is not the published version. Please cite only the published version. この論文は出版社版ではありません。引用の際には出版社版をご確認、ご利用ください。
Graduate School of Biomedical & Health Sciences