title: Mineralized tissue cells are a principal source of FGF23.
abstract: While fibroblast growth factor (FGF) 23 is known as a phosphaturic factor in inherited and/or acquired hypophosphatemic disorders, it also serves an endocrine role in normal phosphate homeostasis. FGF23 acts negatively on the NaPi2a cotransporter and 25-hydroxy D(3)-1 alpha-hydroxylase with a resultant decrease in renal phosphate (Pi) reabsorption, while osteoblasts appear to be a primary source of FGF23 whose expression is counter-upregulated by 1 alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)). Here we have shown the distribution of FGF23 in normal rat bone and tooth, and its expression profile in fetal rat calvaria (RC) cell cultures. FGF23 mRNA was detectable in multiple fetal and adult tissues but levels were much higher in adult calvaria, femur and incisor, compared to the other tissues tested. Immunoreactive FGF23 was predominantly localized to osteoblasts, cementoblasts, and odontoblasts, with sporadic labeling in some chondrocytes, osteocytes and cementocytes. Notably, osteoclasts were also found to be a possible source of FGF23. Fetal bone and tooth germ cells labeled much less intensely than young adult osteoblasts and odontoblasts. In the RC cell model, FGF23 was expressed during osteoblast development. During matrix mineralization induced by beta-glycerophosphate (beta GP), FGF23 expression was transiently upregulated and then decreased to levels lower than in their non-beta GP-treated counterparts. 1,25(OH)(2)D(3) markedly increased FGF23 expression concomitant with the inhibition of beta GP-induced mineralization. Our data suggest that FGF23 expression in bone is closely correlated with bone formation in vitro and vivo, and points towards an important role(s) for FGF23 in young adult but not fetal mineralized tissues as a systemic factor for Pi homeostasis.
authors.affiliation: Department of Oral Growth and Developmental Biology, Hiroshima University Graduate School of Biomedical Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan. yyuji@hiroshima-u.ac.jp
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yoshiko
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.forename: Tomoko
authors.initials: T
authors.lastname: Minamizaki
authors.forename: Chise
authors.initials: C
authors.lastname: Ijuin
authors.forename: Ryoko
authors.initials: R
authors.lastname: Yamamoto
authors.forename: Setsuko
authors.initials: S
authors.lastname: Suemune
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Kozai
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tanne
authors.forename: Jane E
authors.initials: JE
authors.lastname: Aubin
authors.forename: Norihiko
authors.initials: N
authors.lastname: Maeda
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000378:metabolism*; D002478:Cells, Cultured; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012886:Skull / Q000166:cytology / Q000196:embryology; D014070:Tooth / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism*
chemical_list: C505605:Fgf23 protein, rat; D005346:Fibroblast Growth Factors