New Insights into the Roles of Fibroblast Growth Factor 23
First Online: 07 May 2008 DOI:
10.1007/s12018-008-9008-4 Cite this article as: Yoshiko, Y., Minamizaki, T. & Maeda, N. Clinic Rev Bone Miner Metab (2008) 6: 17. doi:10.1007/s12018-008-9008-4 Abstract
Fibroblast growth factor 23 (FGF23) is expressed primarily in skeletal tissues including osteoblasts/osteocytes and acts as a hormone regulating phosphate and vitamin D homeostasis. An excess of active FGF23 in the circulation causes multiple anomalies seen in phosphaturic diseases including rickets/osteomalacia, consistent with some but not all of the phenotypic anomalies seen in FGF23 deficient mice. FGF23 is targeted to kidney and negatively regulates activity/expression of the type II sodium-phosphate cotransporter (NPT2) as well as 25-hydroxy vitamin D-1α-hydroxylase in proximal tubular cells. Recently, teeth have been identified as a possible second principle source of FGF23. Further, both the parathyroid and bone also appear to be functional targets of FGF23: the polypeptide decreases parathyroid hormone (PTH) production and suppresses bone formation in vitro, suggesting a new dimension of FGF23 biology in development and homeostasis. In contrast to other FGF family members, FGF23 requires Klotho, a senescence-related type I membrane protein, for its specific signaling in target organs. However, Klotho expression has not yet been confirmed in skeletal tissues. Nevertheless, similarly to FGF2, FGF23 promotes FGFR1 phosphorylation whose signaling is involved in the negative regulation of bone formation. 1α,25-dihydroxyvitamin D
3 (1,25(OH) 2D) is a potent regulator of FGF23 expression, closely correlated with its inhibitory effect on matrix mineralization. The cleaved extracellular domain of Klotho is known to act as a circulating factor. Therefore, FGF23 may be able to act on multiple tissues including skeletal tissues as a pleiotropic factor, coordinately with or without 1,25(OH) 2D and PTH. Keywords FGF23 Phosphate homeostasis Bone formation Osteoblasts 1,25(OH) 2D PTH Klotho References Clinical Reviews in Bone and Mineral Metabolism
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