Parathyroid hormone regulates fibroblast growth factor-23 in a mouse model of primary hyperparathyroidism.
The importance of fibroblast growth factor 23 (FGF-23) in the pathogenesis of phosphate wasting disorders has been established, but controversy remains about how parathyroid hormone (PTH), which also stimulates urinary phosphate excretion, regulates the circulating level of FGF-23. We found that the serum FGF-23 concentration was higher in PTH-cyclin D1 transgenic mice, a model of primary hyperparathyroidism, than in wild-type mice. The serum FGF-23 concentration was significantly and directly correlated with serum PTH and calcium, and inversely correlated with phosphate levels in 90- to 118-week-old mice (all P < 0.005). Quantitative real-time reverse-transcriptase PCR revealed abundant expression of fgf23 in bone, especially in calvaria. The fgf23 expression in calvaria was significantly higher in the transgenic mice compared to the wild-type mice, and correlated well with serum FGF-23 levels. There was a direct correlation between the expression of fgf23 and the expression of osteocalcin and ALP, suggesting that activation of osteoblasts is important in the regulation of FGF-23. Serum FGF-23 levels decreased in the transgenic mice after parathyroidectomy. In conclusion, PTH plays a major role in the regulation of serum FGF-23 level in primary hyperparathyroidism, likely via activation of osteoblasts in bone.
Kawata
Takehisa
T
Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan.
Imanishi
Yasuo
Y
Kobayashi
Keisuke
K
Miki
Takami
T
Arnold
Andrew
A
Inaba
Masaaki
M
Nishizawa
Yoshiki
Y
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D015870:Gene Expression; D006961:Hyperparathyroidism / Q000097:blood* / Q000503:physiopathology; D051379:Mice; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000378:metabolism; D010281:Parathyroid Hormone / Q000502:physiology*; D016105:Parathyroidectomy; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015415:Biomarkers; C000717428:Fgf23 protein, mouse; D010281:Parathyroid Hormone; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23