title: Fibrous dysplasia and fibroblast growth factor-23 regulation.
abstract: Fibrous dysplasia (FD) is a skeletal disorder caused by activating mutations in Gsα that result in elevations in cAMP. A feature of FD is elevated blood levels of the bone cell-derived phosphaturic hormone, fibroblast growth factor-23 (FGF23). FGF23 regulates serum phosphorus and active vitamin D levels by action on proximal renal tubule cells. An essential step in the production of biologically active FGF23 is glycosylation by the UDP-N-acetyl-α-D-galactosamine:polypeptide N-acetylgalactosaminyl transferase (ppGalNAc-T3). In the absence of glycosylation, FGF23 is processed into inactive N- and C-terminal proteins by a subtilisin proprotein convertase, probably furin. Normally, most if not all circulating FGF23 is intact. In FD, C-terminal levels are elevated, suggesting altered FGF23 processing. Altered processing in FD is the result of a cAMP-dependent, coordinated decrease in ppGalNAc-T3 and an increase in furin enzyme activity. These findings, and emerging data from other diseases, suggest regulation of FGF23 processing may be a physiologically important process.
authors.affiliation: Bone Health Program, Division of Orthopaedics and Sports Medicine, Children's National Medical Center, 111 Michigan Ave NW, Washington, DC 20010, USA. aboyce@childrensnational.org
authors.forename: Alison M
authors.initials: AM
authors.lastname: Boyce
authors.forename: Nisan
authors.initials: N
authors.lastname: Bhattacharyya
authors.forename: Michael T
authors.initials: MT
authors.lastname: Collins
mesh_terms: D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000096:biosynthesis / Q000235:genetics*; D005357:Fibrous Dysplasia of Bone / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D009154:Mutation
chemical_list: C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D004247:DNA