Biology of bone mineralization

Current Opinion in Endocrinology and Diabetes

Volumn 13, Issue 1, 2006, Pages 1-9

  Lian, Jane B ^a  

^a UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

Author keywords

Bone mineralization disorders; Bone quality; Bone sialoprotein; Collagen; Dentin matrix protein 1; Fetuin; Hydroxyapatite; Leucine rich proteins; Matrix Gla protein; Matrix vesicles; Osteocalcin; Osteopontin; Phosphorylated proteins; Pyrophosphate inhibitor

Indexed keywords

CALCITONIN; CALCITRIOL; CALCIUM; HYDROXYAPATITE; PARATHYROID HORMONE; PHOSPHATE;

AGING; ATOMIC FORCE MICROSCOPY; BONE MINERAL; BONE MINERALIZATION; BONE TISSUE; COMPUTER ASSISTED TOMOGRAPHY; CRYSTAL STRUCTURE; GENE MUTATION; GENETIC ANALYSIS; HUMAN; ION TRANSPORT; MEDICAL LITERATURE; METABOLIC DISORDER; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; OSTEOPOROSIS; QUANTITATIVE ANALYSIS; REVIEW;

EID: 33646901009     PISSN: 10683097     EISSN: None     Source Type: Journal    
DOI: 10.1097/01.med.0000200522.41826.af     Document Type: Review

References (112)

1. Follet H, Boivin G, Rumelhart C, Meunier PJ. The degree of mineralization is a determinant of bone strength: a study on human calcanei. Bone 2004; 34:783-789.
2. Tong W, Glimcher MJ, Katz JL, et al. Size and shape of mineralites in young bovine bone measured by atomic force microscopy. Calcif Tissue Int 2003; 72:592-598.
3. Jepsen KJ, Akkus OJ, Majeska RJ, Nadeau JH. Hierarchical relationship between bone traits and mechanical properties in inbred mice. Mamm Genome 2003; 14:97-104.
4. Price C, Herman BC, Lufkin T, et al. Genetic variation in bone growth patterns defines adult mouse bone fragility. J Bone Miner Res 2005; 20:1983-1991.
5. Turner CH, Hsieh YF, Muller R, et al. Genetic regulation of cortical and trabecular bone strength and microstructure in inbred strains of mice. J Bone Miner Res 2000; 15:1126-1131.
6. Turner CH, Hsieh YF, Muller R, et al. Variation in bone biomechanical properties, microstructure, and density in BXH recombinant inbred mice. J Bone Miner Res 2001; 16:206-213.
7. Koller DL, Schriefer J, Sun Q, et al. Genetic effects for femoral biomechanics, structure, and density in C57BL/6J and C3H/HeJ inbred mouse strains. J Bone Miner Res 2003; 18:1758-1765.
8. Yershov Y, Baldini TH, Villagomez S, et al. Bone strength and related traits in HcB/Dem recombinant congenic mice. J Bone Miner Res 2001; 16:992-1003.
9. Boskey AL, Dicarlo E, Paschalis E, et al. Comparison of mineral quality and quantity in iliac crest biopsies from high- and low-turnover osteoporosis: an FT-IR microspectroscopic investigation. Osteoporos Int 2005; [Epub ahead of print].
10. Faibish D, Gomes A, Boivin G, et al. Infrared imaging of calcified tissue in bone biopsies from adults with osteomalacia. Bone 2005; 36:6-12.
11. Paschalis EP, Glass EV, Donley DW, Eriksen EF. Bone mineral and collagen quality in iliac crest biopsies of patients given teriparatide: new results from the fracture prevention trial. J Clin Endocrinol Metab 2005; 90:4644-4649.
12. Cho G, Wu Y, Ackerman JL. Detection of hydroxyl ions in bone mineral by solid-state NMR spectroscopy. Science 2003; 300:1123-1127.
13. Ng AH, Hercz G, Kandel R, Grynpas MD. Association between fluoride, magnesium, aluminum and bone quality in renal osteodystrophy. Bone 2004; 34:216-224.
14. Gollner H, Dani C, Phillips B, et al. Impaired ossification in mice lacking the transcription factor Sp3. Mech Dev 2001; 106:77-83.
15. Lian JB, Javed A, Zaidi SK, et al. Regulatory controls for osteoblast growth and differentiation: role of Runx/Cbfa/AML factors. Crit Rev Eukaryot Gene Expr 2004; 14:1-41.
16. Byers BA, Pavlath GK, Murphy TJ, et al. Cell-type-dependent up-regulation of in vitro mineralization after overexpression of the osteoblast-specific transcription factor Runx2/Cbfal. J Bone Miner Res 2002; 17:1931-1944.
17. Zamurovic N, Cappellen D, Rohner D, Susa M. Coordinated activation of Notch, Wnt and TGF-beta signaling pathways in BMP-2 induced osteogenesis: Notch target gene Hey1 inhibits mineralization and Runx2 transcriptional activity. J Biol Chem 2004; 279:37704-37715.
18. Zaidi SK, Sullivan AJ, Medina R, et al. Tyrosine phosphorylation controls Runx2-mediated subnuclear targeting of YAP to repress transcription. EMBO J 2004; 23:790-799.
19. Cui CB, Cooper LF, Yang X, et al. Transcriptional coactivation of bone-specific transcription factor Cbfa1 by TAZ. Mol Cell Biol 2003; 23:1004-1013.
20. Hong JH, Hwang ES, McManus MT, et al. TAZ, a transcriptional modulator of mesenchymal stem cell differentiation. Science 2005; 309:1074-1078.
21. Gerstenfeld LC, Chipman SD, Glowacki J, Lian JB. Expression of differentiated function by mineralizing cultures of chicken osteoblasts. Dev Biol 1987; 122:49-60.
22. Owen TA, Aronow M, Shalhoub V, et al. Progressive development of the rat osteoblast phenotype in vitro: reciprocal relationships in expression of genes associated with osteoblast proliferation and differentiation during formation of the bone extracellular matrix. J Cell Physiol 1990; 143:420-430.
23. Hanson DA, Eyre DR. Molecular site specificity of pyridinoline and pyrrole cross-links in type I collagen of human bone. J Biol Chem 1996; 271:26508-26516.
24. Glimcher MJ. Mechanism of calcification: role of collagen fibrils and collagen-phosphoprotein complexes in vitro and in vivo. Anat Rec 1989; 224:139-153.
25. Paschalis EP, Verdelis K, Doty SB, et al. Spectroscopic characterization of collagen cross-links in bone. J Bone Miner Res 2001; 16:1821-1828.
26. Glimcher MJ. In: Avioli LV, Krane SM, editors. Metabolic bone disease and clinically related disorders. London: Academic Press; 1998. pp. 23-46.
27. Su X, Sun K, Cui FZ, Landis WJ. Organization of apatite crystals in human woven bone. Bone 2003; 32:150-162.
28. Grabner B, Landis WJ, Roschger P, et al. Age- and genotype-dependence of bone material properties in the osteogenesis imperfecta murine model (oim). Bone 2001; 29:453-457.
29. Fratzl P, Paris O, Klaushofer K, Landis WJ. Bone mineralization in an osteogenesis imperfecta mouse model studied by small-angle x-ray scattering. J Clin Invest 1996; 97:396-402.
30. Misof K, Landis WJ, Klaushofer K, Fratzl P. Collagen from the osteogenesis imperfecta mouse model (oim) shows reduced resistance against tensile stress. J Clin Invest 1997; 100:40-45.
31. Camacho NP, Carroll P, Raggio CL. Fourier transform infrared imaging spectroscopy (FT-IRIS) of mineralization in bisphosphonate-treated oim/oim mice. Calcif Tissue Int 2003; 72:604-609.
32. Stewart TL, Roschger P, Misof BM, et al. Association of COLIA1 Sp1 alleles with defective bone nodule formation in vitro and abnormal bone mineralization in vivo. Calcif Tissue Int 2005; 77:113-118.
33. Murshed M, Harmey D, Millan JL, et al. Unique coexpression in osteoblasts of broadly expressed genes accounts for the spatial restriction of ECM mineralization to bone. Genes Dev 2005; 19:1093-1104. Mice with mineralization defects, the Hyp mouse characterized by hypophosphatemia, the MGP null mouse that results in ectopic calcifications, and the mouse null for Ank, a transmembrane protein required for cellular export of the mineralization inhibitor pyrophosphate (PPi) were used to provide evidence that pyrophosphate is an inhibitor of mineralization and that mineralization occurs in bone as a result of the type I collagen together with unique bone non-collagenous proteins.
34. Price PA, June HH, Hamlin NJ, Williamson MK. Evidence for a serum factor that initiates the re-calcification of demineralized bone. J Biol Chem 2004; 279:19169-19180.
35. Huq NL, Cross KJ, Ung M, Reynolds EC. A review of protein structure and gene organisation for proteins associated with mineralised tissue and calcium phosphate stabilisation encoded on human chromosome 4. Arch Oral Biol 2005; 50:599-609.
36. Fisher LW, Fedarko NS. Six genes expressed in bones and teeth encode the current members of the SIBLING family of proteins. Connect Tissue Res 2003; 44 (Suppl 1):33-40.
37. Svensson L, Narlid I, Oldberg A. Fibromodulin and lumican bind to the same region on collagen type I fibrils. FEBS Lett 2000; 470:178-182.
38. Svensson L, Aszodi A, Reinholt FP, Fassler R, et al. Fibromodulin-null mice have abnormal collagen fibrils, tissue organization, and altered lumican deposition in tendon. J Biol Chem 1999; 274:9636-9647.
39. Svensson L, Heinegard D, Oldberg A. Decorin-binding sites for collagen type I are mainly located in leucine-rich repeats 4-5. J Biol Chem 1995; 270:20712-20716.
40. Sugars RV, Milan AM, Brown JO, et al. Molecular interaction of recombinant decorin and biglycan with type I collagen influences crystal growth. Connect Tissue Res 2003; 44 (Suppl 1):189-195.
41. Young MF, Bi Y, Ameye L, Chen XD. Biglycan knockout mice: new models for musculoskeletal diseases. Glycoconj J 2002; 19:257-262.
42. Ameye L, Young MF. Mice deficient in small leucine-rich proteoglycans: novel in vivo models for osteoporosis, osteoarthritis, Ehlers-Danlos syndrome, muscular dystrophy, and corneal diseases. Glycobiology 2002; 12:107R-116R.
43. Parisuthiman D, Mochida Y, Duarte WR, Yamauchi M. Biglycan modulates osteoblast differentiation and matrix mineralization. J Bone Miner Res 2005; 20:1878-1886.
44. Strandjord TP, Madtes DK, Weiss DJ, Sage EH. Collagen accumulation is decreased in SPARC-null mice with bleomycin-induced pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol 1999; 277:L628-L635.
45. Delany AM, Amling M, Priemel M, et al. Osteopenia and decreased bone formation in osteonectin-deficient mice. J Clin Invest 2000; 105:915-923.
46. Delany AM, Kalajzic I, Bradshaw AD, et al. Osteonectin-null mutation compromises osteoblast formation, maturation, and survival. Endocrinology 2003; 144:2588-2596.
47. Boskey AL, Moore DJ, Amling M, et al. Infrared analysis of the mineral and matrix in bones of osteonectin-null mice and their wildtype controls. J Bone Miner Res 2003; 18:1005-1011.
48. Tye CE, Hunter GK, Goldberg HA. Identification of the type I collagen-binding domain of bone sialoprotein and characterization of the mechanism of interaction. J Biol Chem 2005; 280:13487-13492.
49. Tye CE, Rattray KR, Warner KJ, et al. Delineation of the hydroxyapatite-nucleating domains of bone sialoprotein. J Biol Chem 2003; 278:7949-7955.
50. Gowen LC, Petersen DN, Mansolf AL, et al. Targeted disruption of the osteoblast/osteocyte factor 45 gene (OF45) results in increased bone formation and bone mass. J Biol Chem 2003; 278:1998-2007.
51. Rowe PS. The wrickkened pathways of FGF23, MEPE and PHEX. Crit Rev Oral Biol Med 2004; 15:264-281.
52. Steitz SA, Speer MY, McKee MD, et al. Osteopontin inhibits mineral deposition and promotes regression of ectopic calcification. Am J Pathol 2002; 161:2035-2046.
53. Rittling SR, Matsumoto HN, McKee MD, et al. Mice lacking osteopontin show normal development and bone structure but display altered osteoclast formation in vitro. J Bone Miner Res 1998; 13:1101-1111.
54. Speer MY, McKee MD, Guldberg RE, et al. Inactivation of the osteopontin gene enhances vascular calcification of matrix Gla protein-deficient mice: evidence for osteopontin as an inducible inhibitor of vascular calcification in vivo. J Exp Med 2002; 196:1047-1055.
55. Shapses SA, Cifuentes M, Spevak L, et al. Osteopontin facilitates bone resorption, decreasing bone mineral crystallinity and content during calcium deficiency. Calcif Tissue Int 2003; 73:86-92.
56. Yoshitake H, Rittling SR, Denhardt DT, Noda M. Osteopontin-deficient mice are resistant to ovariectomy-induced bone resorption [published erratum appears in Proc Natl Acad Sci U S A 1999 Sep 14; 96(19):10944]. Proc Natl Acad Sci U S A 1999; 96:8156-8160.
57. Boskey AL, Spevak L, Paschalis E, et al. Osteopontin deficiency increases mineral content and mineral crystallinity in mouse bone. Calcif Tissue Int 2002; 71:145-154.
58. Yang W, Lu Y, Kalajzic I, et al. Dentin matrix protein 1 gene cis-regulation: use in osteocytes to characterize local responses to mechanical loading in vitro and in vivo. J Biol Chem 2005; 280:20680-20690.
59. Ye L, MacDougall M, Zhang S, et al. Deletion of dentin matrix protein-1 leads to a partial failure of maturation of predentin into dentin, hypomineralization, and expanded cavities of pulp and root canal during postnatal tooth development. J Biol Chem 2004; 279:19141-19148.
60. Ling Y, Rios HF, Myers ER, et al. DMP1 depletion decreases bone mineralization in vivo. J Bone Miner Res 2005; 20:2169-2177.
61. Tartaix PH, Doulaverakis M, George A, et al. In vitro effects of dentin matrix protein-1 on hydroxyapatite formation provide insights into in vivo functions. J Biol Chem 2004; 279:18115-18120.
62. Ducy P, Desbois C, Boyce B, et al. Increased bone formation in osteocalcin-deficient mice. Nature 1996; 382:448-452.
63. Rammelt S, Neumann M, Hanisch U, et al. Osteocalcin enhances bone remodeling around hydroxyapatite/collagen composites. J Biomed Mater Res A 2005; 73:284-294.
64. Glowacki J, Rey C, Glimcher MJ, et al. A role for osteocalcin in osteoclast differentiation. J Cell Biochem 1991; 45:292-302.
65. Boskey AL, Gadaleta S, Gundberg C, et al. Fourier transformed infrared microspectroscopic analysis of bones of osteocalcin deficient mice provides insight into the function of osteocalcin. Bone 1998; 23:187.
66. Wu Y, Ackerman JL, Strawich ES, et al. Phosphate ions in bone: identification of a calcium-organic phosphate complex by 31P solid-state NMR spectroscopy at early stages of mineralization. Calcif Tissue Int 2003; 72:610-626.
67. Gericke A, Qin C, Spevak L, et al. Importance of phosphorylation for osteopontin regulation of biomineralization. Calcif Tissue Int 2005; [Epub ahead of print]. This key study showed the importance of protein phosphorylation status for promoting and inhibiting hydroxyapatite formation and provides an example of interaction of non-collagenous proteins in regulating mineral deposition.
68. Beck GR Jr, Knecht N. Osteopontin regulation by inorganic phosphate is ERK1/2-, protein kinase C-, and proteasome-dependent. J Biol Chem 2003; 278:41921-41929.
69. Christensen B, Nielsen MS, Haselmann KF, et al. Post-translationally modified residues of native human osteopontin are located in clusters: identification of 36 phosphorylation and five O-glycosylation sites and their biological implications. Biochem J 2005; 390:285-292.
70. Ritter NM, Farach-Carson MC, Butler WT. Evidence for the formation of a complex between osteopontin and osteocalcin. J Bone Miner Res 1992; 7:877-885.
71. Hunter GK, Poitras MS, Underhill TM, et al. Induction of collagen mineralization by a bone sialoprotein-decorin chimeric protein. J Biomed Mater Res 2001; 55:496-502.
72. Rowe PS, Kumagai Y, Gutierrez G, et al. MEPE has the properties of an osteoblastic phosphatonin and minhibin. Bone 2004; 34:303-319.
73. Silverman L, Boskey AL. Diffusion systems for evaluation of biomineralization. Calcif Tissue Int 2004; 75:494-501.
74. Hunter GK, Hauschka PV, Poole AR, et al. Nucleation and inhibition of hydroxyapatite formation by mineralized tissue proteins. Biochem J 1996; 317 (Pt 1):59-64.
75. Ho AM, Johnson MD, Kingsley DM. Role of the mouse ank gene in control of tissue calcification and arthritis. Science 2000; 289:265-270.
76. Hakim FT, Cranley R, Brown KS, et al. Hereditary joint disorder in progressive ankylosis (ank/ank) mice. I. Association of calcium hydroxyapatite deposition with inflammatory arthropathy. Arthritis Rheum 1984; 27:1411-1420.
77. Waymire KG, Mahuren JD, Jaje JM, et al. Mice lacking tissue non-specific alkaline phosphatase die from seizures due to defective metabolism of vitamin B-6. Nat Genet 1995; 11:45-51.
78. Narisawa S, Frohlander N, Millan JL. Inactivation of two mouse alkaline phosphatase genes and establishment of a model of infantile hypophosphatasia. Dev Dyn 1997; 208:432-446.
79. Fedde KN, Blair L, Silverstein J, et al. Alkaline phosphatase knock-out mice recapitulate the metabolic and skeletal defects of infantile hypophosphatasia. J Bone Miner Res 1999; 14:2015-2026.
80. -/- mice to the Ank/Ank mice, a partial normalization of mineralization phenotypes and PPi levels were found, whereas the double null of NPP1 with Ank/Ank mice resulted in a more severe hypermineralized phenotype. The findings also raise interesting questions as to regulated expression of osteopontin, but importantly illustrate how combined activities from matrix proteins, enzymes and likely other mechanisms are coordinated for the control of mineral deposition.
81. Anderson HC, Sipe JB, Hessle L, et al. Impaired calcification around matrix vesicles of growth plate and bone in alkaline phosphatase-deficient mice. Am J Pathol 2004; 164:841-847. EM and FTIR imaging spectroscopy analyses identified more precisely stages of crystallization through analysis of the matrix vesicles in endochondral bone of tissue non-specific alkaline phosphatase null mice. The ability of the enzyme to cleave pyrophosphate removing the inhibitor is its essential roles and as a consequence of this function generates inorganic phosphate providing a local environment for nucleation and growth of the mineral phase.
82. Anderson HC, Garimella R, Tague SE. The role of matrix vesicles in growth plate development and biomineralization. Front Biosci 2005; 10:822-837.
83. Wennberg C, Hessle L, Lundberg P, et al. Functional characterization of osteoblasts and osteoclasts from alkaline phosphatase knockout mice. J Bone Miner Res 2000; 15:1879-1888.
84. Anderson HC, Harmey D, Camacho NP, et al. Sustained osteomalacia of long bones despite major improvement in other hypophosphatasia-related mineral deficits in tissue nonspecific alkaline phosphatase/nucleotide pyrophosphatase phosphodiesterase 1 double-deficient mice. Am J Pathol 2005; 166:1711-1720.
85. Okawa A, Nakamura I, Goto S, et al. Mutation in Npps in a mouse model of ossification of the posterior longitudinal ligament of the spine. Nat Genet 1998; 19:271-273.
86. Hessle L, Johnson KA, Anderson HC, et al. Tissue-nonspecific alkaline phosphatase and plasma cell membrane glycoprotein-1 are central antagonistic regulators of bone mineralization. Proc Natl Acad Sci U S A 2002; 99:9445-9449.
87. Johnson K, Goding J, Van ED, et al. Linked deficiencies in extracellular PP(i) and osteopontin mediate pathologic calcification associated with defective PC-1 and ANK expression. J Bone Miner Res 2003; 18:994-1004.
88. Price PA, Nguyen TM, Williamson MK. Biochemical characterization of the serum fetuin-mineral complex. J Biol Chem 2003; 278:22153-22160.
89. Schinke T, Amendt C, Trindl A, et al. The serum protein alpha2-HS glyco-protein/fetuin inhibits apatite formation in vitro and in mineralizing calvaria cells. A possible role in mineralization and calcium homeostasis. J Biol Chem 1996; 271:20789-20796.
90. Jahnen-Dechent W, Schinke T, Trindl A, et al. Cloning and targeted deletion of the mouse fetuin gene. J Biol Chem 1997; 272:31496-31503.
91. Schilling AF, Schinke T, Munch C, et al. Increased bone formation in mice lacking apolipoprotein E. J Bone Miner Res 2005; 20:274-282.
92. Newman P, Bonello F, Wierzbicki AS, et al. The uptake of lipoprotein-borne phylloquinone (vitamin K1) by osteoblasts and osteoblast-like cells: role of heparan sulfate proteoglycans and apolipoprotein E. J Bone Miner Res 2002; 17:426-433.
93. Luo G, Ducy P, McKee MD, et al. Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein. Nature 1997; 386:78-81.
94. Murshed M, Schinke T, McKee MD, Karsenty G. Extracellular matrix mineralization is regulated locally; different roles of two gla-containing proteins. J Cell Biol 2004; 165:625-630. By demonstrating the consequences of rescue of the MGP null phenotype by crossing with transgenic mice overexpressing either MGP or osteocalcin, the distinct functional activities of the calcium binding gla residues in osteocalcin (bone related gla protein) and matrix gla protein (cartilage, kidney and vascular calcification inhibitor protein) were established.
95. Fraser JD, Price PA. Lung, heart, and kidney express high levels of mRNA for the vitamin K- dependent matrix Gla protein. Implications for the possible functions of matrix Gla protein and for the tissue distribution of the gamma-carboxylase. J Biol Chem 1988; 263:11033-11036.
96. Boskey AL, Karsenty G, McKee MD. Chemistry and biology of mineralized tissues. Goldberg M, Boskey A, Robinson C, editors. Chicago: American Academy of Orthopaedic Surgeons; 2000. pp. 63-67.
97. Hough TA, Bogani D, Cheeseman MT, et al. Activating calcium-sensing receptor mutation in the mouse is associated with cataracts and ectopic calcification. Proc Natl Acad Sci U S A 2004; 101:13566-13571.
98. Yoshizawa T, Handa Y, Uematsu Y, et al. Mice lacking the vitamin D receptor exhibit impaired bone formation, uterine hypoplasia and growth retardation after weaning. Nat Genet 1997; 16:391-396.
99. Amling M, Priemel M, Holzmann T, et al. Rescue of the skeletal phenotype of vitamin D receptor-ablated mice in the setting of normal mineral ion homeostasis: formal histomorphometric and biomechanical analyses. Endocrinology 1999; 140:4982-4987.
100. Li YC, Amling M, Pirro AE, et al. Normalization of mineral ion homeostasis by dietary means prevents hyperparathyroidism, rickets, and osteomalacia, but not alopecia in vitamin D receptor-ablated mice. Endocrinology 1998; 139:4391-4396.
101. Li YC, Pirro AE, Amling M, et al. Targeted ablation of the vitamin D receptor: an animal model of vitamin D-dependent rickets type II with alopecia. Proc Natl Acad Sci U S A 1997; 94:9831-9835.
102. Misof BM, Roschger P, Tesch W, et al. Targeted overexpression of vitamin D receptor in osteoblasts increases calcium concentration without affecting structural properties of bone mineral crystals. Calcif Tissue Int 2003; 73:251-257.
103. Yee YK, Chintalacharuvu SR, Lu J, Nagpal S. Vitamin D receptor modulators for inflammation and cancer. Mini Rev Med Chem 2005; 5:761-778.
104. Bielesz B, Klaushofer K, Oberbauer R. Renal phosphate loss in hereditary and acquired disorders of bone mineralization. Bone 2004; 35:1229-1239.
105. Bai X, Miao D, Panda D, et al. Partial rescue of the Hyp phenotype by osteoblast-targeted PHEX (phosphate-regulating gene with homologies to endopeptidases on the X chromosome) expression. Mol Endocrinol 2002; 16:2913-2925.
106. Miao D, Bai X, Panda D, et al. Osteomalacia in hyp mice is associated with abnormal phex expression and with altered bone matrix protein expression and deposition. Endocrinology 2001; 142:926-939.
107. Erben RG, Mayer D, Weber K, et al. Overexpression of human PHEX under the human beta-actin promoter does not fully rescue the Hyp mouse phenotype. J Bone Miner Res 2005; 20:1149-1160.
108. Shimada T, Muto T, Urakawa I, et al. Mutant FGF-23 responsible for autosomal dominant hypophosphatemic rickets is resistant to proteolytic cleavage and causes hypophosphatemia in vivo. Endocrinology 2002; 143:3179-3182.
109. Berndt T, Craig TA, Bowe AE, et al. Secreted frizzled-related protein 4 is a potent tumor-derived phosphaturic agent. J Clin Invest 2003; 112:785-794.
110. Larsson T, Marsell R, Schipani E, et al. Transgenic mice expressing fibroblast growth factor 23 under the control of the alpha1 (I) collagen promoter exhibit growth retardation, osteomalacia, and disturbed phosphate homeostasis. Endocrinology 2004; 145:3087-3094.
111. Shimada T, Yamazaki Y, Takahashi M, et al. Vitamin D receptor-independent FGF23 actions in regulating phosphate and vitamin D metabolism. Am J Physiol Renal Physiol 2005; 289:F1088-F1095.
112. Dunstan CR, Zhou H, Seibel MJ. Fibroblast growth factor 23: a phosphatonin regulating phosphate homeostasis? Endocrinology 2004; 145:3084-3086.