The wrickkened pathways of FGF23, MEPE and PHEX

Critical Reviews in Oral Biology and Medicine

Volumn 15, Issue 5, 2004, Pages 264-281

  Rowe, Peter S N ^a  

^a UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO   (United States)

Author keywords

FGF23; Hypophosphatemia; MEPE; Mineralization; Osteomalacia; PHEX; Phosphaturic; Rickets

Indexed keywords

CALCIUM PHOSPHATE; ENZYME; FIBROBLAST GROWTH FACTOR 23; GLYCOPROTEIN; MATRIX EXTRACELLULAR PHOSPHOGLYCOPROTEIN; METALLOPROTEINASE; OSTEOPONTIN; PHOSPHATE REGULATING GENE WITH HOMOLOGIES TO ENDOPEPTIDASES ON THE X CHROMOSOME ENZYME; STATHERIN; UNCLASSIFIED DRUG; FIBROBLAST GROWTH FACTOR; MEPE PROTEIN, HUMAN; ONCOPROTEIN; PHEX PROTEIN, HUMAN; PHEX PROTEIN, MOUSE; PHOSPHATE; PHOSPHATE REGULATING NEUTRAL ENDOPEPTIDASE; PHOSPHOPROTEIN; PROTEIN; SCLEROPROTEIN; SFRP4 PROTEIN, HUMAN; SFRP4 PROTEIN, MOUSE;

AUTOSOMAL DOMINANT HYPOPHOSPHATEMIC RICKETS; BONE MINERALIZATION; GENE MUTATION; HUMAN; NONHUMAN; ONCOGENIC HYPOPHOSPHATEMIC OSTEOMALACIA; OSSIFICATION; OSTEOMALACIA; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN MOTIF; REVIEW; RICKETS; TOOTH DEVELOPMENT; VITAMIN D RESISTANT RICKETS; ANIMAL; GENETICS; HYPOPHOSPHATEMIA; METABOLISM; MOUSE; MOUSE MUTANT; MUTATION; OSTEOSARCOMA;

ANIMALS; CALCIFICATION, PHYSIOLOGIC; EXTRACELLULAR MATRIX PROTEINS; FIBROBLAST GROWTH FACTORS; GLYCOPROTEINS; HUMANS; HYPOPHOSPHATEMIA, FAMILIAL; MICE; MICE, MUTANT STRAINS; MUTATION; OSTEOMALACIA; OSTEOSARCOMA; PHEX PHOSPHATE REGULATING NEUTRAL ENDOPEPTIDASE; PHOSPHATES; PHOSPHOPROTEINS; PROTEINS; PROTO-ONCOGENE PROTEINS;

EID: 11244352700     PISSN: 10454411     EISSN: None     Source Type: Journal    
DOI: 10.1177/154411130401500503     Document Type: Review

References (174)

1. Aisa MC, Rahman S, Senin U, Maggio D, Russell RG (1996). Cathepsin B activity in normal human osteoblast-like cells and human osteoblastic osteosarcoma cells (MG-63): regulation by interleukin-1 beta and parathyroid hormone. Biochim Biophys Acta 1290:29-36.
2. Aisa MC, Beccari T, Costanzi E, Maggio D (2003). Cathepsin B in osteoblasts. Biochim Biophys Acta 1621:149-159.
3. Allen HC, Fedarko NS, Jain A, Whybro A, Barker ME, Eastell R, et al. (2003). The response of MEPE to long-term and short-term phosphate supplementation in healthy volunteers (abstract). J Bone Miner Res 18:S116
4. Argiro L, Desbarats M, Glorieux FH, Ecarot B (2001). Mepe, the gene encoding a tumor-secreted protein in oncogenic hypophosphatemic osteomalacia, is expressed in bone. Genomics 74:342-351.
5. Aschinberg LC, Solomon LM, Zeis PM, Justice P, Rosenthal IM (1977). Vitamin D-resistant rickets associated with epidermal nevus syndrome: demonstration of a phosphaturic substance in the dermal lesions. J Pediatr 91:56-60.
6. Azam N, Zhang MY, Wang X, Tenenhouse HS, Portale AA (2003). Disordered regulation of renal 25-hydroxyvitamin D-1alpha-hydroxylase gene expression by phosphorus in X-linked hypophosphatemic (hyp) mice. Endocrinology 144:3463-3468.
7. Bai X, Miao D, Panda D, Grady S, McKee MD, Goltzman D, et al. (2002). Partial rescue of the Hyp phenotype by osteoblast-targeted PHEX (Phosphate-Regulating Gene with Homologies to Endopeptidases on the X Chromosome) expression. Mol Endocrinol 16:2913-2925.
8. Bai XY, Miao D, Goltzman D, Karaplis AC (2003). The autosomal dominant hypophosphatemic rickets R176Q mutation in FGF23 resists proteolytic cleavage and enhances in vivo biological potency. J Biol Chem 278:9843-9849.
9. Barrett AJ (1995). Proteolytic enzymes: aspartic and metallo peptidases. In: Methods in enzymology. Vol. 248. 1st ed. Barrett AJ, ed. New York: Academic Press, pp. 1-873.
10. Beaumont A, Le Moual H, Boileau G, Crine P, Roques BP (1991). Evidence that both arginine 102 and arginine 747 are involved in substrate binding to neutral endopeptidase (EC 3.4.24.11). J Biol Chem 266:214-220.
11. Beaumont A, Barbe B, Le Moual H, Boileau G, Crine P, Fournie-Zaluski MC, et al. (1992). Charge polarity reversal inverses the specificity of neutral endopeptidase-24.11. J Biol Chem 267:2138-2141.
12. Beck L, Soumounou Y, Martel J, Krishnamurthy G, Gauthier C, Goodyer CG, et al. (1997). Pex/PEX tissue distribution and evidence for a deletion in the 3′ region of the Pex gene in X-linked hypophosphatemic mice. J Clin Invest 99:1200-1209.
13. Beck L, Karaplis AC, Amizuka N, Hewson AS, Ozawa H, Tenenhouse HS (1998). Targeted inactivation of Npt2 in mice leads to severe renal phosphate wasting, hypercalciuria, and skeletal abnormalities. Proc Natl Acad Sci USA 95:5372-5377.
14. Bennick A, McLaughlin AC, Grey AA, Madapallimattam G (1981). The location and nature of calcium-binding sites in salivary acidic proline-rich phosphoproteins. J Biol Chem 256:4741-4746.
15. Berndt T, Craig TA, Bowe AE, Vassiliadis J, Reczek D, Finnegan R, et al. (2003). Secreted frizzled-related protein 4 is a potent tumor-derived phosphaturic agent. J Clin Invest 112:785-794.
16. Bianchetti L, Oudet C, Poch O (2002). M13 endopeptidases: new conserved motifs correlated with structure, and simultaneous phylogenetic occurrence of PHEX and the bony fish. Proteins 47:481-488.
17. Blydt-Hansen TD, Tenenhouse HS, Goodyer P (1999). PHEX expression in parathyroid gland and parathyroid hormone dysregulation in X-linked hypophosphatemia. Pediatric Nephrol 13:607-611.
18. Boileau G, Tenenhouse HS, DesGroseillers L, Crine P (2001). Characterization of PHEX endopeptidase catalytic activity: identification of parathyroid-hormone-related peptide 107-139 as a substrate and osteocalcin, PPi and phosphate as inhibitors. Biochem J 355:707-713.
19. Bonjour JP, Trechsel U, Fleisch H, Schenk R, DeLuca HF, Baxter LA (1975). Action of 1,25-dihydroxyvitamin D3 and a diphosphonate on calcium metabolism in rats. Am J Physiol 229:402-408.
20. Boskey AL, Spevak L, Paschalis E, Doty SB, McKee MD (2002). Osteopontin deficiency increases mineral content and mineral crystallinity in mouse bone. Calcif Tissue Int 71:145-154.
21. Bowe AE, Finnegan R, Jan de Beur SM, Cho J, Levine MA, Kumar R, et al. (2001). FGF-23 inhibits renal tubular phosphate transport and is a PHEX substrate. Biochem Biophys Res Commun 284:977-981.
22. Brewer AJ, Canaff L, Hendy GN, Tenenhouse HS, Gauthier C, Chau H, et al. (2003). Differential regulation of PHEX expression in bone and parathyroid gland by chronic renal insufficiency and 1,25-dihydroxyvitamin D3. Am J Physiol Renal Physiol 286:F739-F748.
23. Cai Q, Hodgson SF, Kao PC, Lennon VA, Klee GG, Zinsmiester AR, et al. (1994). Brief report: inhibition of renal phosphate transport by a tumor product in a patient with oncogenic osteomalacia. N Engl J Med 330:1645-1649.
24. Campos M, Couture C, Hirata IY, Juliano MA, Loisel TP, Crine P, et al. (2003). Human recombinant endopeptidase PHEX has a strict S1′ specificity for acidic residues and cleaves peptides derived from fibroblast growth factor-23 and matrix extracellular phosphoglycoprotein. Biochem J 373:271-279.
25. Carpenter TO, Moltz KC, Ellis B, Andreoli M, McCarthy TL, Centrella M, et al. (1998). Osteocalcin production in primary osteoblast cultures derived from normal and Hyp mice. Endocrinology 139:35-43.
26. Chingwen L, Hersh LB (1995). Neprilysin: assay methods, purification, and characterisation. In: Methods in enzymology. Vol. 248. Proteolytic enzymes: aspartic and metallo peptidases. 1st ed. Barrett AJ, ed. New York: Academic Press, pp. 253-263.
27. De Beur SM, Finnegan RB, Vassiliadis J, Cook B, Barberio D, Estes S, et al. (2002). Tumors associated with oncogenic osteomalacia express genes important in bone and mineral metabolism. J Bone Miner Res 17:1102-1110.
28. Dion N, Le Moual H, Crine P, Boileau G (1993). Kinetic evidence that His-711 of neutral endopeptidase 24.11 is involved in stabilization of the transition state. FEBS Lett 318:301-304.
29. Dion N, Le Moual H, Fournie-Zaluski MC, Roques BP, Crine P, Boileau G, et al. (1995). Evidence that Asn542 of neprilysin (EC 3.4.24.11) is involved in binding of the P2′ residue of substrates and inhibitors. Biochem J 311:623-627.
30. Dobbie H, Shirley DG, Faria NJ, Rowe PSN, Slater JM, Unwin RJ (2003). Infusion of the bone-derived protein MEPE causes phosphaturia in rats (abstract). J Am Soc Nephrol 14:468A.
31. Drezner MK (2001). Tumor-induced osteomalacia. Rev Endocr Metab Disord 2:175-186.
32. Drezner MK (2003). Hypophosphatemic rickets. Endocr Dev 6:126-155.
33. Du L, Desbarats M, Viel J, Glorieux FH, Cawthorn C, Ecarot B (1996). cDNA cloning of the murine Pex gene implicated in X-linked hypophosphatemia and evidence for expression in bone. Genomics 36:22-28.
34. Dubois SG, Ruchon AF, Delalandre A, Boileau G, Lajeunesse D (2002). Role of abnormal neutral endopeptidase-like activities in Hyp mouse bone cells in renal phosphate transport. Am J Physiol Cell Physiol 283:C1414-C1421.
35. Ecarot B, Desbarats M (1999). 1,25-(OH)(2)D-3 down-regulates expression of Phex, a marker of the mature osteoblast. Endocrinology 140:1192-1199.
36. Ecarot B, Glorieux FH, Desbarats M, Travers R, Labelle L (1992a). Defective bone formation by Hyp mouse bone cells transplanted into normal mice: evidence in favor of an intrinsic osteoblast defect. J Bone Miner Res 7:215-220.
37. Ecarot FH, Glorieux FH, Desbarats M, Travers R, Labelle L (1992b). Effect of dietary phosphate deprivation and supplementation of recipient mice on bone formation by transplanted cells from normal and X-linked hypophosphataemic mice. J Bone Miner Res 7:523-530.
38. Ecarot B, Caverzasio J, Desbarats M, Bonjour JP, Glorieux FH (1994). Phosphate transport by osteoblasts from X-linked hypophosphatemic mice. Am J Physiol 266:E33-E38.
39. Ecarot B, Glorieux FH, Desbarats M, Travers R, Labelle L (1995). Effect of 1,25-dihydroxyvitamin D3 treatment on bone formation by transplanted cells from normal and X-linked hypophosphatemic mice. J Bone Miner Res 10:424-431.
40. Ecarot-Charrier B, Glorieux FH, Travers R, Desbarats M, Bouchard F, Hinek A (1988). Defective bone formation by transplanted Hyp mouse bone cells into normal mice. Endocrinology 123:768-773.
41. Econs MJ, Drezner MK (1994). Tumour induced osteomalacia - unveiling a new hormone. N Engl J Med 330:1679-1681.
42. Erben RG, Maye D, Weber K, Johnson T, Jonsson K, Jüppner H, et al. (2003). Ubiquitous overexpression of Phex does not fully rescue the Hyp mouse phenotype (abstract). J Bone Miner Res 18:S22.
43. Fisher LW, Torchia DA, Fohr B, Young MF, Fedarko NS (2001). Flexible structures of SIBLING proteins, bone sialoprotein, and osteopontin. Biochem Biophys Res Commun 280:460-465.
44. Francis F, Strom TM, Hennig S, Boeddrich A, Lorenz B, Brandau O, et al. (1997). Genomic organisation of the human PEX gene mutated in X-linked dominant hypophosphataemic rickets. Gen Res 7:573-585.
45. Fujiwara I, Aravindan R, Horst RL, Drezner MK (2003). Abnormal regulation of renal 25-hydroxyvitamin D-1alpha-hydroxylase activity in X-linked hypophosphatemia: a translational or posttranslational defect. J Bone Miner Res 18:434-442.
46. Fukumoto S, Yamashita T (2002). Fibroblast growth factor-23 is the phosphaturic factor in tumor-induced osteomalacia and may be phosphatonin. Curr Opin Nephrol Hypertens 11:385-389.
47. Glisson F, Bate G, Regemorter A (1651). A treatise of the rickets: being a disease common to children. Peter Cole, Cornhill Royal Exchange. London: Bedford Royal Infirmary Medical Library.
48. Gowen LC, Petersen DN, Mansolf AL, Qi H, Stock JL, Tkalcevic GT, et al. (2003). Targeted disruption of the osteoblast/osteocyte factor 45 gene (OF45) results in increased bone formation and bone mass. J Biol Chem 278:1998-2007.
49. Guo R, Quarles LD (1997). Cloning and sequencing of human PEX from a bone cDNA library: evidence for its developmental stage-specific regulation in osteoblasts. J Bone Miner Res 12:1009-1017.
50. Guo R, Liu S, Spurney RF, Quarles LD (2001). Analysis of recombinant Phex: an endopeptidase in search of a substrate. Am J Physiol Endocrinol Metab 281:E837-E847.
51. Guo R, Rowe PS, Liu S, Simpson LG, Xiao ZS, Quarles LD (2002). Inhibition of MEPE cleavage by Phex. Biochem Biophys Res Commun 297:38-45.
52. Gururaja TL, Levine MJ (1996). Solid-phase synthesis and characterization of human salivary statherin: a tyrosine-rich phosphoprotein inhibitor of calcium phosphate precipitation. Pept Res 9:283-289.
53. Halstead LR, Weinstein RS, Cheng SL, Rifas L, Avioli LV (1996). Comparison of 22-oxacalcitriol and 1,25(OH)2D3 on bone metabolism in young X-linked hypophosphatemic male mice. Am J Physiol 270:E141-E147.
54. Hoyer JR, Asplin JR, Otvos L (2001). Phosphorylated osteopontin peptides suppress crystallization by inhibiting the growth of calcium oxalate crystals. Kidney Int 60:77-82.
55. Huang H, Ye L, Xie Y, Ko S, Harris SE, Bonewald L, et al. (2003). Bone repair is dramatically delayed in dentin matrix protein-1 (Dmp1) deficient mice (abstract). J Bone Miner Res 18:S197.
56. HYP Consortium, Francis F, Hennig S, Korn B, Reinhardt R, de Jong D, et al. (1995). Agene (PEX) with homologies to endopeptidases is mutated in patients with X-linked hypophosphatemic rickets. The HYP Consortium. Nat Genet 11:130-136.
57. Jain A, Fedarko NS, Collins MT, Gelman R, Ankrom MA, Tayback M, et al. (2004). Serum levels of matrix extracellular phosphoglycoprotein (MEPE) in normal humans correlate with serum phosphorus, parathyroid hormone and bone mineral density. J Clin Endocrinol Metab 89:4158-4161.
58. Jan de Beur SM, Levine MA (2002). Molecular pathogenesis of hypophosphatemic rickets. J Clin Endocrinol Metab 87:2467-2473.
59. Jo OD, Shih R, Sun A, Pham P, Yanagawa J, Yanagawa N (2000). Cathepsin D (Cat D) and bone defect in hypophosphatemic (Hyp) mice (abstract). J Am Soc Nephrol 11:408A.
60. Jo OD, Yang F, Kuizon B, Shih HM, Yanagawa N (2001). Increased apoptosis in Hyp mouse bone. Potential role of cathepsin D (abstract). J Am Soc Nephrol 12:743A.
61. Jonsson KB, Mannstadt M, Miyauchi A, Yang IM, Stein G, Ljunggren O, et al. (2001). Extracts from tumors causing oncogenic osteomalacia inhibit phosphate uptake in opossum kidney cells. J Endocrinol 169:613-620.
62. Jonsson KB, Zahradnik R, Larsson T, White KE, Sugimoto T, Imanishi Y, et al. (2003). Fibroblast growth factor 23 in oncogenic osteomalacia and X-linked hypophosphatemia. N Engl J Med 348:1656-1663.
63. Kay GF, Thakker RV, Rastan S (1991). Generation of a Mus spretus/Mus domesticus backcross segregating for Ta and Hyp by in vitro fertilisation (abstract). Cytogenet Cell Genet 58:2137.
64. Kronenberg HM (2002). NPT2a - the key to phosphate homeostasis. N Engl J Med 347:1022-1024.
65. Kumar R (2002). New insights into phosphate homeostasis: fibroblast growth factor 23 and frizzled-related protein-4 are phosphaturic factors derived from tumors associated with osteomalacia. Curr Opin Nephrol Hypertens 11:547-553.
66. Lajeunesse D, Meyer RA Jr, Hamel L (1996). Direct demonstration of a humorally-mediated inhibition of renal phosphate transport in the Hyp mouse. Kidney Int 50:1531-1538.
67. Larsson T, Nisbeth U, Ljunggren O, Juppner H, Jonsson KB (2003). Circulating concentration of FGF-23 increases as renal function declines in patients with chronic kidney disease, but does not change in response to variation in phosphate intake in healthy volunteers. Kidney Int 64:2272-2279.
68. Le Moual H, Devault A, Roques BP, Crine P, Boileau G (1991). Identification of glutamic acid 646 as a zinc-coordinating residue in endopeptidase-24.11. J Biol Chem 266:15670-15674.
69. Le Moual H, Beaumont A, Roques BP, Crine P, Boileau G (1992a). Identification of two arginine residues involved in the binding of substrate to neutral endopeptidase 24-11. Matrix Suppl 1:99.
70. Le Moual H, Crine P, Boileau G (1992b). Identification of Glu 646 of neutral endopeptidase 24-11 as a zinc binding residue. Matrix Suppl 1:100.
71. Le Moual H, Roques BP, Crine P, Boileau G (1993). Substitution of potential metal-coordinating amino acid residues in the zinc-binding site of endopeptidase-24.11. FEBS Lett 324:196-200.
72. Le Moual H, Dion N, Roques BP, Crine P, Boileau G (1994). Asp650 is crucial for catalytic activity of neutral endopeptidase 24-11. Eur J Biochem 221:475-480.
73. Lee S, Lin M, Mele A, Cao Y, Farmar J, Russo D, et al. (1999). Proteolytic processing of big endothelin-3 by the Kell blood group protein. Blood 94:1440-1450.
74. Lee S, Russo D, Redman CM (2000). The Kell blood group system: Kell and XK membrane proteins. Sem Hematol 37:113-121.
75. Lee S, Debnath AK, Redman CM (2003). Active amino acids of the Kell blood group protein and model of the ectodomain based on the structure of neutral endopeptidase 24.11. Blood 102:3028-3034.
76. Letarte M, Vera S, Tran R, Addis JB, Onizuka RJ, Quackenbush EJ, et al. (1988). Common acute lymphocytic leukemia antigen is identical to neutral endopeptidase. J Exp Med 168:1247-1253.
77. Liu S, Guo R, Quarles LD (2001). Cloning and characterization of the proximal murine phex promoter. Endocrinology 142:3987-3995.
78. Liu S, Guo R, Tu Q, Quarles LD (2002). Overexpression of Phex in osteoblasts fails to rescue the Hyp mouse phenotype. J Biol Chem 277:3686-3697.
79. Liu S, Guo R, Simpson LG, Xiao ZS, Burnham CE, Quarles LD (2003a). Regulation of FGF23 expression but not degradation by phex. J Biol Chem 278:37419-37426.
80. Liu S, Guo R, Xiao G, Quarles LD (2003b). Regulation of FGF23 expression but not metabolism by Phex (abstract). J Bone Miner Res 18:S50.
81. Liu S, Brown TA, Xiao Z, Guo R, Quarles LD (2003c). Deletion of Mepe in Hyp mice fails to correct hypophosphatemia but partially rescues abnormal mineralization ex vivo (abstract). J Bone Miner Res 18:S24.
82. Loghman-Adham M, Dousa TP (1992). Dual action of phosphonoformic acid on Na(+)-phosphate cotransport in opossum kidney cells. Am J Physiol 263:F301-F310.
83. Loghman-Adham M, Szczepanska-Konkel M, Yusufi AN, Van Scoy M, Dousa TP (1987). Inhibition of Na+-Pi cotransporter in small gut brush border by phosphonocarboxylic acids. Am J Physiol 252:G244-G249.
84. Loghman-Adham M, Szczepanska-Konkel M, Dousa TP (1992). Phosphate transport in brush border membranes from uremic rats. Response to phosphonoformic acid. J Am Soc Nephrol 3:1253-1259.
85. Long JR, Dindot JL, Zebroski H, Kiihne S, Clark RH, Campbell AA, et al. (1998). Apeptide that inhibits hydroxyapatite growth is in an extended conformation on the crystal surface. Proc Natl Acad Sci USA 95:12083-12087.
86. Lyon MF (1988). X-chromosome inactivation and the location and expression of X-linked genes. Am J Hum Genet 42:8-16.
87. MacDougall M, Simmons D, Gu TT, Dong J (2002). MEPE/OF45, a new dentin/bone matrix protein and candidate gene for dentin diseases mapping to chromosome 4q21. Connect Tissue Res 43:320-330.
88. Marie-Claire C, Tiraboschi G, Ruffet E, Inguimbert N, Fournie-Zaluski MC, Roques BP (2000). Exploration of the S(′)(1) subsite of neprilysin: a joined molecular modeling and site-directed mutagenesis study. Proteins 39:365-371.
89. McCloskey EV, Yates AJ, Gray RE, Hamdy NA, Galloway J, Kanis JA (1988). Diphosphonates and phosphate homeostasis in man. Clin Sci (Lond) 74:607-612.
90. Meyer MH, Meyer RA Jr (2000). MRNA expression of Phex in mice and rats: the effect of low phosphate diet. Endocrine 13:81-87.
91. Meyer RA Jr, Meyer MA, Gray RW (1989a). Parabiosis suggests a humoral factor is involved in X-linked hypophosphataemia in mice. J Bone Miner Res 4:493-500.
92. Meyer RA Jr, Tenenhouse HS, Meyer MA, Klugerman AH (1989b). The renal phosphate transport defect in normal mice parabiosed to X-linked hypophosphataemic mice persists after parathyroidectomy. J Bone Miner Res 4:523-532.
93. Meyer RA, Young CG, Meyer MH, Garges PL, Price DK (2000). Effect of age on the expression of Pex (Phex) in the mouse. Calcif Tissue Int 66:282-287.
94. Miao D, Bai X, Panda D, McKee M, Karaplis A, Goltzman D (2001). Osteomalacia in hyp mice is associated with abnormal phex expression and with altered bone matrix protein expression and deposition. Endocrinology 142:926-939.
95. Miao D, Bai X, Panda D, Karaplis AC, Goltzman D, McKee MD (2004). Cartilage abnormalities are associated with abnormal Phex expression and with altered matrix protein and MMP-9 localization in Hyp mice. Bone 34:638-647.
96. Miyauchi A, Fukase M, Tsutsumi M, Fujita T (1988). Hemangiopericytoma induced osteomalacia: tumour transplantation in nude mice causes hypophosphataemia and tumour extracts inhibit renal 25-hydroxyvitamin D α1-hydroxylase activity. J Clin Endocrinol Metab 67:46-53.
97. Muhlbauer RC, Bonjour JP, Fleisch H (1981). Tubular handling of phosphate along the nephron of thyroparathyroidectomized rats injected with ethane-1-hydroxy-1,1-diphosphonate. Clin Sci (Lond) 60:171-177.
98. Nelson AE, Namkung HJ, Patava J, Wilkinson MR, Chang AM, Reddel RR, et al. (1996). Characteristics of tumor cell bioactivity in oncogenic osteomalacia. Molec Cell Endocrinol 124:17-23.
99. Nelson AE, Robinson BG, Hogan JJ, Dwight T, Mason RS (1997). Mechanism of inhibition of renal phosphate uptake by a tumor-derived factor in oncogenic osteomalacia (abstract). J Bone Miner Res 12:F679.
100. Nelson AE, Mason RS, Hogan JJ, Diamond T, Robinson BG (1998). Tumor expression studies indicate that HEM-1 is unlikely to be the active factor in oncogenic osteomalacia. Bone 23:549-553.
101. Nelson AE, Hogan JJ, Holm IA, Robinson BG, Mason RS (2001). Phosphate wasting in oncogenic osteomalacia: PHEX is normal and the tumor-derived factor has unique properties. Bone 28:430-439.
102. Nesbitt T, Coffman TM, Griffiths R, Drezner MK (1992). Crosstransplantation of kidneys in normal and Hyp mice. Evidence that the Hyp mouse phenotype is unrelated to an intrinsic renal defect. J Clin Invest 89:1453-1459.
103. Nesbitt T, Econs MJ, Byun JK, Martel J, Tenenhouse HS, Drezner MK (1995). Phosphate transport in immortalized cell cultures from the renal proximal tubule of normal and Hyp mice: evidence that the HYP gene locus product is an extrarenal factor. J Bone Miner Res 10:1327-1333.
104. Nesbitt T, Fujiwara I, Thomas R, Xiao ZS, Quarles LD, Drezner MK (1999). Coordinated maturational regulation of PHEX and renal phosphate transport inhibitory activity: evidence for the pathophysiological role of PHEX in X-linked hypophosphatemia. J Bone Miner Res 14:2027-2035.
105. Oefner C, D'Arcy A, Hennig M, Winkler FK, Dale GE (2000). Structure of human neutral endopeptidase (neprilysin) complexed with phosphoramidon. J Mol Biol 296:341-349.
106. Okano T, Tsugawa N, Hirami C, Kato S (2003). Functional properties of cultured normal and vitamin D receptor knockout mice calvarial osteoblasts (abstract). J Bone Miner Res 18:S141.
107. Oursler MJ, Riggs BL, Spelsberg TC (1993). Glucocorticoid-induced activation of latent transforming growth factor-beta by normal human osteoblast-like cells. Endocrinology 133:2187-2196.
108. Petersen DJ, Boniface AM, Schranck FW, Rupich RC, Whyte MP (1992). X-linked hypophosphataemic rickets: a study with (literature review) of linear growth response to calcitriol and phosphate therapy. J Bone Miner Res 7:583-597.
109. Petersen DN, Tkalcevic GT, Mansolf AL, Rivera-Gonzalez R, Brown TA (2000). Identification of osteoblast/osteocyte factor 45 (OF45), a bone-specific cDNA encoding an RGD-containing protein that is highly expressed in osteoblasts and osteocytes. J Biol Chem 275:36172-36180.
110. Popovtzer MM (1981). Tumour induced hypophosphataemic osteomalacia: evidence for a phosphaturic cyclic AMP-independent action of tumour extract (abstract). Clin Res 29:418A.
111. Qiu ZQ, Tenenhouse HS, Scriver CR (1993). Parental origin of mutant allele does not explain absence of gene dose effect in X-linked Hyp mice. Genet Res Camb 62:39-43.
112. Qiu ZQ, Travers R, Rauch F, Glorieux FH, Scriver CR, Tenenhouse HS (2003). Effect of gene dose and parental origin on bone histomorphometry in X-linked Hyp mice. Bone 34:134-139.
113. Quarles LD (2003). FGF23, PHEX, and MEPE regulation of phosphate homeostasis and skeletal mineralization. Am J Physiol Endocrinol Metab 285:E1-E9.
114. Quarles LD, Drezner MK (2001). Pathophysiology of X-linked hypophosphatemia, tumor-induced osteomalacia, and autosomal dominant hypophosphatemia: a perPHEXing problem. J Clin Endocrinol Metab 86:494-496.
115. Raj PA, Johnsson M, Levine MJ, Nancollas GH (1992). Salivary statherin. Dependence on sequence, charge, hydrogen bonding potency, and helical conformation for adsorption to hydroxyapatite and inhibition of mineralization. J Biol Chem 267:5968-5976.
116. Rawlings ND, Barrett AJ (1995). Evolutionary families of metallopeptidases. Methods Enzymol 248:183-228.
117. Rawlings ND, Barrett AJ (1999). MEROPS: the peptidase database. Nucleic Acids Res 27:325-331.
118. Rifas L, Gupta A, Hruska KA, Avioli LV (1995). Altered osteoblast gluconeogenesis in X-linked hypophosphatemic mice is associated with a depressed intracellular pH. Calcif Tissue Int 57:60-63.
119. Rifas L, Cheng S, Halstead LR, Gupta A, Hruska KA, Avioli LV (1997). Skeletal casein kinase activity defect in the HYP mouse. Calcif Tissue Int 61:256-259.
120. Riminucci M, Collins MT, Fedarko NS, Cherman N, Corsi A, White KE, et al. (2003). FGF-23 in fibrous dysplasia of bone and its relationship to renal phosphate wasting. J Clin Invest 112:683-692.
121. Rowe PS (1994). Molecular biology of hypophosphataemic rickets and oncogenic osteomalacia. Hum Genet 94:457-467.
122. Rowe PS (1997). The PEX gene: its role in X-linked rickets, osteomalacia, and bone mineral metabolism. Exp Nephrol 5:355-363.
123. Rowe PS (1998). The role of the PHEX gene (PEX), in families with X-linked hypophosphataemic rickets. Curr Opin Nephrol Hypertens 7:367-376.
124. Rowe PS, Goulding JN, Francis F, Oudet C, Econs MJ, Hanauer A, et al. (1996a). The gene for X-linked hypophosphataemic rickets maps to a 200-300 kb region in Xp22.1, and is located on a single YAC containing a putative vitamin D response element (VDRE). Hum Genet 97:345-352.
125. Rowe PS, Ong A, Cockerill F, Goulding J, Hewison M (1996b). Candidate 56 and 58 kDa protein(s) responsible for mediating the renal defects in oncogenic hypophosphataemic osteomalacia. Bone 18:159-169.
126. Rowe PS, Oudet C, Francis F, Sinding C, Pannetier S, Econs MJ, et al. (1997). Distribution of mutations in the PEX gene in families with X-linked hypophosphataemic rickets (HYP). Hum Mol Genet 6:539-549.
127. Rowe PS, de Zoysa P, Dong R, Wang H, White K, Econs MJ, et al. (2000). MEPE, a new gene expressed in bone-marrow and tumours causing osteomalacia. Genomics 67:54-68.
128. Rowe PS, Kumagai Y, Gutierrez G, Garrett IR, Blacher R, Rosen D, et al. (2004). MEPE has the properties of an osteoblastic phosphatonin and minhibin. Bone 34:303-319.
129. Roy S, Martel J, Ma S, Tenenhouse HS (1994). Increased renal 25-hydroxyvitamin D3-24-hydroxylase messenger ribonucleic acid and immunoreactive protein in phosphate deprived Hyp mice: a mechanism for accelerated 1,25-dihydroxyvitamin D3 catabolism in X-linked hypophosphataemic rickets. Endocrinology 134:1761-1767.
130. Ruchon AF, Marcinkiewicz M, Siegfried G, Tenenhouse HS, DesGroseillers L, Crine P, et al. (1998). Pex mRNA is localized in developing mouse osteoblasts and odontoblasts. J Histochem Cytochem 46:459-468.
131. Ruchon AF, Marcinkiewicz M, Ellefsen K, Basak A, Aubin J, Crine P, et al. (2000a). Cellular localization of neprilysin in mouse bone tissue and putative role in hydrolysis of osteogenic peptides. J Bone Miner Res 15:1266-1274.
132. Ruchon AF, Tenenhouse HS, Marcinkiewicz M, Siegfried G, Aubin JE, Desgroseillers L, et al. (2000b). Developmental expression and tissue distribution of Phex protein: effect of the Hyp mutation and relationship to bone markers. J Bone Miner Res 15:1440-1450.
133. Sabbagh Y, Jones AO, Tenenhouse HS (2000). PHEXdb, a locus-specific database for mutations causing X-linked hypophosphatemia. Hum Mutat 16:1-6.
134. Sabbagh Y, Boileau G, DesGroseillers L, Tenenhouse HS (2001). Disease-causing missense mutations in the PHEX gene interfere with membrane targeting of the recombinant protein. Hum Mol Genet 10:1539-1546.
135. Sabbagh Y, Boileau G, Campos M, Carmona AK, Tenenhouse HS (2003). Structure and function of disease-causing missense mutations in the PHEX gene. J Clin Endocrinol Metab 88:2213-2222.
136. Saito H, Kusano K, Kinosaki M, Ito H, Hirata M, Segawa H, et al. (2003). Human fibroblast growth factor-23 mutants suppress Na+-dependent phosphate co-transport activity and 1alpha,25-dihydroxyvitamin D3 production. J Biol Chem 278:2206-2211.
137. Schlesinger DH, Hay DI (1977). Complete covalent structure of statherin, a tyrosine-rich acidic peptide which inhibits calcium phosphate precipitation from human parotid saliva. J Biol Chem 252:1689-1695.
138. Schwartz SS, Hay DI, Schluckebier SK (1992). Inhibition of calcium phosphate precipitation by human salivary statherin: structure-activity relationships. Calcif Tissue Int 50:511-517.
139. Schweizer A, Valdenaire O, Koster A, Lang Y, Schmitt G, Lenz B, et al. (1999). Neonatal lethality in mice deficient in XCE, a novel member of the endothelin-converting enzyme and neutral endopeptidase family [In Process Citation]. J Biol Chem 274:20450-20456.
140. Scriver CR, Tenenhouse HS (1992). X-linked hypophosphataemia: a homologous phenotype in humans and mice with unusual organ-specific gene dosage. J Inherit Metab Dis 15:610-624.
141. Segawa H, Kawakami E, Kaneko I, Kuwahata M, Ito M, Kusano K, et al. (2003). Effect of hydrolysis-resistant FGF23-R179Q on dietary phosphate regulation of the renal type-II Na/Pi transporter. Pflügers Arch 446:585-592.
142. Seufert J, Ebert K, Muller J, Eulert J, Hendrich C, Werner E, et al. (2001). Octreotide therapy for tumor-induced osteomalacia. N Engl J Med 345:1883-1888.
143. Shetty NS, Meyer RA Jr (1991). Craniofacial abnormalities in mice with X-linked hypophosphatemic genes (Hyp or Gy). Teratology 44:463-472.
144. Shih NR, Jo OD, Yanagawa N (2002). Effects of PHEX antisense in human osteoblast cells. J Am Soc Nephrol 13:394-399.
145. Shimada T, Mizutani S, Muto T, Yoneya T, Hino R, Takeda S, et al. (2001). Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia. Proc Natl Acad Sci USA 98:6500-6505.
146. Shimada T, Muto T, Urakawa I, Yoneya T, Yamazaki Y, Okawa K, et al. (2002). Mutant FGF-23 responsible for autosomal dominant hypophosphatemic rickets is resistant to proteolytic cleavage and causes hypophosphatemia in vivo. Endocrinology 143:3179-3182.
147. Shimada T, Hasegawa H, Yamazaki Y, Muto T, Hino R, Takeuchi Y, et al. (2004). FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis. J Bone Miner Res 19:429-435.
148. Shipp MA, Richardson NE, Sayre PH, Brown NR, Masteller EL, Clayton LK, et al. (1988). Molecular cloning of the common acute lymphoblastic leukemia antigen (CALLA) identifies a type II integral membrane protein. Proc Natl Acad Sci USA 85:4819-4823.
149. Singh RJ, Kumar R (2003). Fibroblast growth factor 23 concentrations in humoral hypercalcemia of malignancy and hyperparathyroidism. Mayo Clin Proc 78:826-829.
150. Strewler GJ (2001). FGF23, hypophosphatemia, and rickets: has phosphatonin been found? Proc Natl Acad Sci USA 98:5945-5946.
151. Tamaki N, Tada T, Morita M, Watanabe T (2002). Comparison of inhibitory activity on calcium phosphate precipitation by acidic proline-rich proteins, statherin, and histatin-1. Calcif Tissue Int 71:59-62.
152. Tenenhouse HS (1999). Recent advances in epithelial sodium-coupled phosphate transport. Curr Opin Nephrol Hypertens 8:407-414.
153. Tenenhouse HS, Murer H (2003). Disorders of renal tubular phosphate transport. J Am Soc Nephrol 14:240-248.
154. Tenenhouse HS, Martel J, Gauthier C, Segawa H, Miyamoto KI (2003). Differential effects of Npt2a gene ablation and the X-linked Hyp mutation on renal expression of type IIc Na/Pi cotransporter. Am J Physiol Renal Physiol 285:F1271-F1278.
155. Thompson DL, Sabbagh Y, Tenenhouse HS, Roche PC, Drezner MK, Salisbury JL, et al. (2002). Ontogeny of Phex/PHEX protein expression in mouse embryo and subcellular localization in osteoblasts. J Bone Miner Res 17:311-320.
156. Trechsel U, Schenk R, Bonjour JP, Russell RG, Fleisch H (1977). Relation between bone mineralization, Ca absorption, and plasma Ca in phosphonate-treated rats. Am J Physiol 232:E298-E305.
157. Turner AJ, Tanzawa K (1997). Mammalian membrane metallopeptidases: NEP, ECE, KELL, and PEX. FASEB J 11:355-364.
158. Turner AJ, Isaac RE, Coates D (2001). The neprilysin (NEP) family of zinc metalloendopeptidases: genomics and function. Bioessays 23:261-269.
159. Valdenaire O, Schweizer A (2000). Endothelin-converting enzyme-like I (ECELI; 'XCE'): a putative metallopeptidase crucially involved in the nervous control of respiration. Biochem Soc Trans 28:426-430.
160. Valdenaire O, Rohrbacher E, Langeveld A, Schweizer A, Meijers C (2000). Organization and chromosomal localization of the human ECEL1 (XCE) gene encoding a zinc metallopeptidase involved in the nervous control of respiration. Biochem J 346:611-616.
161. VanScoy M, Loghman-Adham M, Onsgard M, Szczepanska-Konkel M, Homma S, Knox FG, et al. (1988). Mechanism of phosphaturia elicited by administration of phosphonoformate in vivo. Am J Physiol 255:F984-F994.
162. Walton RJ, Russell RG, Smith R (1975). Changes in the renal and extrarenal handling of phosphate induced by disodium etidronate (EHDP) in man. Clin Sci Mol Med 49:45-56.
163. Wang L, Du L, Ecarot B (1999). Evidence for Phex haploinsufficiency in murine X-linked hypophosphatemia. Mamm Genome 10:385-389.
164. Weber TJ, Liu S, Indridason OS, Quarles LD (2003). Serum FGF23 levels in normal and disordered phosphorus homeostasis. J Bone Miner Res 18:1227-1234.
165. Wesson JA, Johnson RJ, Mazzali M, Beshensky AM, Stietz S, Giachelli C, et al. (2003). Osteopontin is a critical inhibitor of calcium oxalate crystal formation and retention in renal tubules. J Am Soc Nephrol 14:139-147.
166. White KE, Evans WE, O'Riordan JLH, Speer MC, Econs MJ, Lorenz-Depiereux B, et al. (2000). Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23. Nat Genet 26:345-348.
167. White KE, Jonsson KB, Carn G, Hampson G, Spector TD, Mannstadt M, et al. (2001). The autosomal dominant hypophosphatemic rickets (ADHR) gene is a secreted polypeptide overexpressed by tumors that cause phosphate wasting. J Clin Endocrinol Metab 86:497-500.
168. Whyte MP, Schranck FW, Armamento-Villareal R (1996). X-linked hypophosphatemia: a search for gender, race, anticipation, or parent of origin effects on disease expression in children. J Clin Endocrinol Metab 81:4075-4080.
169. Wilkins GE, Granleese S, Hegele RG, Holden J, Anderson DW, Bondy GP (1995). Oncogenic osteomalacia: evidence for a humoral phosphaturic factor. J Clin Endocrinol Metab 80:1628-1634.
170. Xiao ZS, Crenshaw M, Guo R, Nesbitt T, Drezner MK, Quarles LD (1998). Intrinsic mineralization defect in Hyp mouse osteoblasts. Am J Physiol 275:E700-E708.
171. Yamamoto T, Ecarot B, Glorieux FH (1992). Abnormal response of osteoblasts from Hyp mice to 1,25-dihydroxyvitamin D3. Bone 13:209-215.
172. Yamashita T, Yoshioka M, Itoh N (2000). Identification of a novel fibroblast growth factor, FGF-23, preferentially expressed in the ventrolateral thalamic nucleus of the brain. Biochem Biophys Res Commun 277:494-498.
173. Yamashita T, Konishi M, Miyake A, Inui KI, Itoh N (2002). Fibroblast growth factor (FGF)-23 inhibits renal phosphate reabsorption by activation of the mitogen-activated protein kinase pathway. J Biol Chem 277:28265-28270.
174. Yamazaki Y, Okazaki R, Shibata M, Hasegawa Y, Satoh K, Tajima T, et al. (2002). Increased circulatory level of biologically active full-length FGF-23 in patients with hypophosphatemic rickets/osteomalacia. J Clin Endocrinol Metab 87:4957-4960.