title: The EP4-ERK-dependent pathway stimulates osteo-adipogenic progenitor proliferation resulting in increased adipogenesis in fetal rat calvaria cell cultures.
abstract: We previously reported that fetal rat calvaria (RC) cells are osteo-adipogenic bipotential and that PGE(2) receptors EP2 and EP4 are involved in bone nodule formation via both common and distinct MAPK pathways in RC cell cultures. Because PGE(2) participates in multiple biological processes including adipogenesis, it is of interest to determine the additional role(s) of PGE(2) in RC cells. PGE(2) 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 PGE(2)-EP4-ERK pathway increases the number of osteo-adipogenic bipotential progenitor cells, with a resultant increase in adipogenesis in RC cell cultures.
authors.affiliation: Department of Oral Growth and Developmental Biology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima 734-8553, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Minamizaki
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yoshiko
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Yoshioka
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Kozai
authors.forename: Jane E
authors.initials: JE
authors.lastname: Aubin
authors.forename: Norihiko
authors.initials: N
authors.lastname: Maeda
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D050156:Adipogenesis / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D020935:MAP Kinase Signaling System / Q000502:physiology*; D010012:Osteogenesis; D051381:Rats; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000378:metabolism*; D012886:Skull / Q000166:cytology* / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D058309:Receptors, Prostaglandin E, EP4 Subtype