FGF-23 in fibrous dysplasia of bone and its relationship to renal phosphate wasting.
FGF-23, a novel member of the FGF family, is the product of the gene mutated in autosomal dominant hypophosphatemic rickets (ADHR). FGF-23 has been proposed as a circulating factor causing renal phosphate wasting not only in ADHR (as a result of inadequate degradation), but also in tumor-induced osteomalacia (as a result of excess synthesis by tumor cells). Renal phosphate wasting occurs in approximately 50% of patients with McCune-Albright syndrome (MAS) and fibrous dysplasia of bone (FD), which result from postzygotic mutations of the GNAS1 gene. We found that FGF-23 is produced by normal and FD osteoprogenitors and bone-forming cells in vivo and in vitro. In situ hybridization analysis of FGF-23 mRNA expression identified "fibrous" cells, osteogenic cells, and cells associated with microvascular walls as specific cellular sources of FGF-23 in FD. Serum levels of FGF-23 were increased in FD/MAS patients compared with normal age-matched controls and significantly higher in FD/MAS patients with renal phosphate wasting compared with those without, and correlated with disease burden bone turnover markers commonly used to assess disease activity. Production of FGF-23 by FD tissue may play an important role in the renal phosphate-wasting syndrome associated with FD/MAS.
Riminucci
Mara
M
Dipartmento di Medicina Sperimentale e Patologia, Università dell'Aquila, Italy.
Collins
Michael T
MT
Fedarko
Neal S
NS
Cherman
Natasha
N
Corsi
Alessandro
A
White
Kenneth E
KE
Waguespack
Steven
S
Gupta
Anurag
A
Hannon
Tamara
T
Econs
Michael J
MJ
Bianco
Paolo
P
Gehron Robey
Pamela
P
D000293:Adolescent; D000328:Adult; D001842:Bone and Bones / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood / Q000235:genetics / Q000502:physiology*; D005357:Fibrous Dysplasia of Bone / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008875:Middle Aged; D010710:Phosphates / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis
C000717427:FGF23 protein, human; D010710:Phosphates; D012333:RNA, Messenger; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23