title: Expression of FGF23 is correlated with serum phosphate level in isolated fibrous dysplasia.
abstract: Fibrous dysplasia (FD) patients sometimes suffer from concomitant hypophosphatemic rickets/osteomalacia, resulting from renal phosphate wasting. It was recently reported that FD tissue in the patients with McCune-Albright syndrome (MAS) expressed fibroblast growth factor-23 (FGF-23), which is now known to be as a pathogenic phosphaturic factor in patients with oncogenic osteomalacia and X-linked hypophosphatemic rickets. Since it remains controversial whether serum phosphate levels are influenced by FGF23 expressions in FD tissue, isolated FD patients without MAS syndrome were examined for the relationship between FGF23 expressions, circulating levels of FGF-23 and phosphate to negate the effects of MAS-associated endocrine abnormalities on serum phosphate. Eighteen paraffin embedded FD tissues and 2 frozen tissues were obtained for the study. Sixteen of 18 isolated FD tissues were successfully analyzed GNAS gene, which exhibited activated mutations observed in MAS. Eight of 16 FD tissues, which exhibited GNAS mutations, revealed positive staining for FGF-23. These evidence indicate that postzygotic activated mutations of GNAS is necessary for the FD tissue formation by mosaic distribution of mutated osteogenic cell lineage, but is not sufficient to elevate FGF23 expression causing generalized osteomalacia with severe renal phosphate wasting. The expression level of FGF23 in isolated FD tissue with hypophosphatemic osteomalacia determined by real-time PCR was abundant close to the levels in OOM tumors. Osteoblasts/osteocytes in woven bone were predominant source of circulating FGF-23 in FD tissues by immunohistochemistry. A negative correlation of the intensity of FGF-23 staining with serum inorganic phosphate levels indicated that the expression of FGF23 in focal FD tissues could be a prominent determinant of serum phosphate levels in isolated FD patient. These data provide novel insights into the regulatory mechanism of serum inorganic phosphate levels in isolated FD patients and extend the notion that FGF-23 originating from FD tissue may cause hypophosphatemia not only in isolated FD patients but also in the patients with MAS syndrome.
authors.affiliation: Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Imanishi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Koshiyama
authors.forename: Akimitsu
authors.initials: A
authors.lastname: Miyauchi
authors.forename: Kenichi
authors.initials: K
authors.lastname: Wakasa
authors.forename: Takehisa
authors.initials: T
authors.lastname: Kawata
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Goto
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Ohashi
authors.forename: Hajime M
authors.initials: HM
authors.lastname: Koyano
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Mochizuki
authors.forename: Takami
authors.initials: T
authors.lastname: Miki
authors.forename: Masaaki
authors.initials: M
authors.lastname: Inaba
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Nishizawa
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002864:Chromogranins; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000235:genetics*; D005357:Fibrous Dysplasia of Bone / Q000097:blood / Q000235:genetics*; D005359:Fibrous Dysplasia, Polyostotic / Q000097:blood / Q000235:genetics / Q000378:metabolism; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D016612:Paraffin Embedding; D010710:Phosphates / Q000097:blood*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D002864:Chromogranins; C000717427:FGF23 protein, human; D010710:Phosphates; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs