UCSD Nature Molecule Pages
Published online: 30 Mar 2006 | doi:10.1038/mp.a003934.01
Basis Sequence: Mouse
Franz J Jakob1, Regina Ebert2, Jochen R Seufert3
1Orthopaedic Department, Experimental and Clinical Osteology, D-97074, DE. 2Orthopedic Department, University of Wuerzburg, 97074, DE. 3Medizinische Poliklinik, University of Wuerzburg, 97070, DE.
Correspondence should be addressed to Franz J Jakob: email@example.com
FGF23 is a secreted member of the fibroblast growth factor family as concluded by structural similarities with other family members. Its function was delineated by its characterization as a causative factor of renal phosphate wasting in tumor-induced osteomalacia. FGF23 belongs to the group of phosphatonins, which regulate phosphate metabolism. FGF23 was shown to enhance renal phosphate excretion by down-regulating the sodium-phosphate transporter NPT2, to inhibit renal 25-hydroxy-vitamin D3 1α hydroxylase and to inhibit phosphate uptake in the intestine. The latter could also be an indirect effect exerted by the reduced 1,25 vitamin D3 synthesis and consecutive reduction of the vitamin D3 stimulated intestinal phosphate uptake. The combination of enhanced renal phosphate wasting and impaired intestinal absorption may cause substantial negative phosphate balance. Tumor induced osteomalacia (TIO) is an acquired syndrome of FGF23 overproduction caused by mostly benign mesenchymal tumors overexpressing and secreting FGF23 besides other phosphatonins. A recent report describes high serum FGF23 levels in patients with malignant ovarian tumors. FGF23 expression in other cell type tumors, such as mixed connective tissue tumor, angiodysplasia, osteoblastic osteosarcoma and in linear nevus sebaceous have been reported. FGF23 knock out animals developed high serum phosphate and 1,25 vitamin D3 levels with enhanced renal phosphate absorption. These mice showed an abnormal bone phenotype with severe growth retardation, impaired growth plate organization, low bone mineral density and shortened life span. In contrast, transgenic mice overexpressing FGF23 and animals with FGF23 overproducing tumors showed hypophosphatemia, low 1,25 vitamin D3 serum levels and rachitic bone. Transplantation of FGF23 overexpressing tumor cells caused a syndrome which resembled tumor-induced osteomalacia. Little is known about putative autocrine effects on mesenchymal precursor cells and paracrine effects in the bone microenvironment.
Alternative names for this molecule:
FGF-23; Fgf23; Fibroblast growth factor 23