| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on March 20, 2002
Accepted on August 22, 2002
1 Division of Endocrinology, Department of Medicine, and Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montréal, QC, Canada H3T 1E2, Calcium Research Laboratory, Department of Medicine, McGill University Health Centre and McGill University, Montréal, QC, Canada H3A 1A1, Faculty of Dentistry, and Department of Anatomy and Cell Biology, McGill University, Montréal, QC, Canada H3A 2B2
* To whom correspondence should be addressed. E-mail: akarapli{at}ldi.jgh.mcgill.ca.
Inactivating mutations and/or deletions of PHEX/Phex are responsible for X-linked hypophosphatemic rickets (XLH) in humans and in the murine homologue, Hyp. The predominant osteoblastic expression of Phex has implicated a primary metabolic osteoblast defect in the pathophysiology of this disorder. By targeting PHEX expression to osteoblasts in the Hyp genetic background, we aimed to correct the corresponding biochemical and morphological abnormalities and obtain information on their pathogenetic mechanism. When transgene Phex expression, driven by a mouse pro-
1(I) collagen gene promoter, was crossed into the Hyp background, it improved the defective mineralization of bone and teeth but failed to correct the hypophosphatemia and altered vitamin D metabolism associated with the disorder. Ex-vivo bone marrow cultures confirmed the amelioration in the Hyp-associated matrix mineralization defect after Phex expression. These findings suggest that while the Hyp bone and teeth abnormalities partially correct after PHEX gene transfer, additional factors and/or sites of PHEX expression are likely critical for the elaboration of the appropriate molecular signals that alter renal phosphate handling and vitamin D metabolism in this disorder.
This article has been cited by other articles:
 |
|
 |
|
  A. Martin, V. David, J. S. Laurence, P. M. Schwarz, E. M. Lafer, A.-M. Hedge, and P. S. N. Rowe Degradation of MEPE, DMP1, and Release of SIBLING ASARM-Peptides (Minhibins): ASARM-Peptide(s) Are Directly Responsible for Defective Mineralization in HYP Endocrinology, April 1, 2008; 149(4): 1757 - 1772. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Bai, D. Miao, D. Goltzman, and A. C. Karaplis Early Lethality in Hyp Mice with Targeted Deletion of Pth Gene Endocrinology, October 1, 2007; 148(10): 4974 - 4983. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Liu and L. D. Quarles How Fibroblast Growth Factor 23 Works J. Am. Soc. Nephrol., June 1, 2007; 18(6): 1637 - 1647. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Onishi, R. Okawa, T. Ogawa, S. Shintani, and T. Ooshima Phex Mutation Causes the Reduction of Npt2b mRNA in Teeth Journal of Dental Research, February 1, 2007; 86(2): 158 - 162. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. E. White, T. E. Larsson, and M. J. Econs The Roles of Specific Genes Implicated as Circulating Factors Involved in Normal and Disordered Phosphate Homeostasis: Frizzled Related Protein-4, Matrix Extracellular Phosphoglycoprotein, and Fibroblast Growth Factor 23 Endocr. Rev., May 1, 2006; 27(3): 221 - 241. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Schipani, A. Zallone, G. J. Strewler, J. W. Pike, S. Ferrari, Y. Jiang, and E. Seeman Meeting Report from the 27th Annual Meeting of the American Society for Bone and Mineral Research: September 23-27, 2005 in Nashville, Tennessee, USA IBMS BoneKEy, January 1, 2006; 3(1): 29 - 62. [Full Text] [PDF]
|
|
|
|
 |
|
 N. Matsumoto, O. D. Jo, R. N. J. Shih, E. J. Brochmann, S. S. Murray, V. Hong, J. Yanagawa, and N. Yanagawa Increased cathepsin D release by Hyp mouse osteoblast cells Am J Physiol Endocrinol Metab, July 1, 2005; 289(1): E123 - E132. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Liu, T. A. Brown, J. Zhou, Z.-S. Xiao, H. Awad, F. Guilak, and L. D. Quarles Role of Matrix Extracellular Phosphoglycoprotein in the Pathogenesis of X-Linked Hypophosphatemia J. Am. Soc. Nephrol., June 1, 2005; 16(6): 1645 - 1653. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Bresler, J. Bruder, K. Mohnike, W. D Fraser, and P. S N Rowe Serum MEPE-ASARM-peptides are elevated in X-linked rickets (HYP): implications for phosphaturia and rickets J. Endocrinol., December 1, 2004; 183(3): R1 - R9. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. R. Hines, O. I. Kolek, M. D. Jones, S. H. Serey, N. B. Sirjani, P. R. Kiela, P. W. Jurutka, M. R. Haussler, J. F. Collins, and F. K. Ghishan 1,25-Dihydroxyvitamin D3 Down-regulation of PHEX Gene Expression Is Mediated by Apparent Repression of a 110 kDa Transfactor That Binds to a Polyadenine Element in the Promoter J. Biol. Chem., November 5, 2004; 279(45): 46406 - 46414. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Bai, D. Miao, J. Li, D. Goltzman, and A. C. Karaplis Transgenic Mice Overexpressing Human Fibroblast Growth Factor 23 (R176Q) Delineate a Putative Role for Parathyroid Hormone in Renal Phosphate Wasting Disorders Endocrinology, November 1, 2004; 145(11): 5269 - 5279. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. S.N. Rowe THE WRICKKENED PATHWAYS OF FGF23, MEPE AND PHEX Critical Reviews in Oral Biology & Medicine, September 1, 2004; 15(5): 264 - 281. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Miao, J. Li, Y. Xue, H. Su, A. C. Karaplis, and D. Goltzman Parathyroid Hormone-Related Peptide Is Required for Increased Trabecular Bone Volume in Parathyroid Hormone-Null Mice Endocrinology, August 1, 2004; 145(8): 3554 - 3562. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Qin, O. Baba, and W.T. Butler POST-TRANSLATIONAL MODIFICATIONS OF SIBLING PROTEINS AND THEIR ROLES IN OSTEOGENESIS AND DENTINOGENESIS Critical Reviews in Oral Biology & Medicine, May 1, 2004; 15(3): 126 - 136. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. K. Panda, D. Miao, I. Bolivar, J. Li, R. Huo, G. N. Hendy, and D. Goltzman Inactivation of the 25-Hydroxyvitamin D 1{alpha}-Hydroxylase and Vitamin D Receptor Demonstrates Independent and Interdependent Effects of Calcium and Vitamin D on Skeletal and Mineral Homeostasis J. Biol. Chem., April 16, 2004; 279(16): 16754 - 16766. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Miao, B. He, B. Lanske, X.-Y. Bai, X.-K. Tong, G. N. Hendy, D. Goltzman, and A. C. Karaplis Skeletal Abnormalities in Pth-Null Mice Are Influenced by Dietary Calcium Endocrinology, April 1, 2004; 145(4): 2046 - 2053. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Brewer, L. Canaff, G. N. Hendy, and H. S. Tenenhouse Differential regulation of PHEX expression in bone and parathyroid gland by chronic renal insufficiency and 1,25-dihydroxyvitamin D3 Am J Physiol Renal Physiol, April 1, 2004; 286(4): F739 - F748. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Vargas, M. St-Louis, L. Desgroseillers, J.-L. Charli, and G. Boileau Parathyroid Hormone-Related Protein(1-34) Regulates Phex Expression in Osteoblasts through the Protein Kinase A Pathway Endocrinology, November 1, 2003; 144(11): 4876 - 4885. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. D. Quarles FGF23, PHEX, and MEPE regulation of phosphate homeostasis and skeletal mineralization Am J Physiol Endocrinol Metab, July 1, 2003; 285(1): E1 - E9. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
