title: FGF Suppresses Poldip2 Expression in Osteoblasts.
abstract: Osteoporosis is one of the most prevalent ageing-associated diseases that are soaring in the modern world. Although various aspects of the disease have been investigated to understand the bases of osteoporosis, the pathophysiological mechanisms underlying bone loss is still incompletely understood. Poldip2 is a molecule that has been shown to be involved in cell migration of vascular cells and angiogenesis. However, expression of Poldip2 and its regulation in bone cells were not known. Therefore, we examined the Poldip2 mRNA expression and the effects of bone regulators on the Poldip2 expression in osteoblasts. We found that Poldip2 mRNA is expressed in osteoblastic MC3T3-E1 cells. As FGF controls osteoblasts and angiogenesis, FGF regulation was investigated in these cells. FGF suppressed the expression of Poldip2 in MC3T3-E1 cells in a time dependent manner. Protein synthesis inhibitor but not transcription inhibitor reduced the FGF effects on Poldip2 gene expression in MC3T3-E1 cells. As for bone-related hormones, dexamethasone was found to enhance the expression of Poldip2 in osteoblastic MC3T3-E1 cells whereas FGF still suppressed such dexamethasone effects. With respect to function, knockdown of Poldip2 by siRNA suppressed the migration of MC3T3-E1 cells. Poldip2 was also expressed in the primary cultures of osteoblast-enriched cells and FGF also suppressed its expression. Finally, Poldip2 was expressed in femoral bone in vivo and its levels were increased in aged mice compared to young adult mice. These data indicate that Poldip2 is expressed in osteoblastic cells and is one of the targets of FGF. J. Cell. Biochem. 118: 1670-1677, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.|Department of Oral Maxillofacial Surgery, School of Dentistry, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Sakie
authors.initials: S
authors.lastname: Katsumura
authors.affiliation: Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Izu
authors.affiliation: Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Department of Medicine, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Kathy
authors.initials: K
authors.lastname: Griendling
authors.affiliation: Department of Oral Maxillofacial Surgery, School of Dentistry, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Harada
authors.affiliation: Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.|Yokohama City Minato Red Cross Hospital, Yokohama, Japan.|Department of Orthopedic Surgery, School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Noda
authors.affiliation: Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ezura
mesh_terms: D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; C514737:mitogenin 1 protein, mouse; D005346:Fibroblast Growth Factors
keywords: FGF; OSTEOBLAST; POLDIP2