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Pediatric Nephrology

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01.11.2012 | Educational Review

Phosphate homeostasis and its role in bone health

verfasst von: Maria Goretti M. G. Penido, Uri S. Alon

Erschienen in: Pediatric Nephrology | Ausgabe 11/2012

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Abstract

Phosphate is one of the most abundant minerals in the body, and its serum levels are regulated by a complex set of processes occurring in the intestine, skeleton, and kidneys. The currently known main regulators of phosphate homeostasis include parathyroid hormone (PTH), calcitriol, and a number of peptides collectively known as the “phosphatonins” of which fibroblast growth factor-23 (FGF-23) has been best defined. Maintenance of extracellular and intracellular phosphate levels within a narrow range is important for many biological processes, including energy metabolism, cell signaling, regulation of protein synthesis, skeletal development, and bone integrity. The presence of adequate amounts of phosphate is critical for the process of apoptosis of mature chondrocytes in the growth plate. Without the presence of this mineral in high enough quantities, chondrocytes will not go into apoptosis, and the normal physiological chain of events that includes invasion of blood vessels and the generation of new bone will be blocked, resulting in rickets and delayed growth. In the rest of the skeleton, hypophosphatemia will result in osteomalacia due to an insufficient formation of hydroxyapatite. This review will address phosphate metabolism and its role in bone health.

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Marks J, Edward S, Debnam ES, Unwi RJ (2010) Phosphate homeostasis and the renal-gastrointestinal axis. Am J Physiol Renal Physiol 299:F285–F296PubMedCrossRef

Berndt T, Thomas LF, Craig TA, Sommer S, Li X, Bergstralh EJ, Kumar R (2007) Evidence for a signaling axis by which intestinal phosphate rapidly modulates renal phosphate reabsorption. Proc Natl Acad Sci USA 104:11085–11090PubMedCrossRef

Shaikh A, Berndt T, Kumar R (2008) Regulation of phosphate homeostasis by the phosphatonins and other novel mediators. Pediatr Nephrol 23:1203–1210PubMedCrossRef

Giral H, Caldas Y, Sutherland E, Wilson P, Breusegem SY, Barry N, Blaine J, Jiang T, Wang XX, Levi M (2009) Regulation of the rat intestinal Na-dependent phosphate transporters by dietary phosphate. Am J Physiol Renal Physiol 297:F1466–F1475PubMedCrossRef

Reining SC, Liesegang A, Betz H, Biber J, Murer H, Hernando N (2010) Expression of renal and intestinal Na/Pi cotransporters in the absence of GABARAP. Pflügers Arch 460:201–217CrossRef

Ramon I, Kleynen P, Jean-Jacques Body J, Karmali R (2010) Fibroblast growth factor 23 and its role in phosphate homeostasis. Eur J Endocrinol 162:1–10PubMedCrossRef

Gattineni J, Baum M (2010) Regulation of phosphate transport by fibroblast growth factor 23 (FGF-23): implications for disorders of phosphate metabolism. Pediatr Nephrol 25:591–601PubMedCrossRef

Amanzadeh J, Reilly RF Jr (2006) Hypophosphatemia: an evidence-based approach to its clinical consequences and management. Nat Clin Pract Nephrol 2:136–148PubMedCrossRef

Tiosano D, Hochberg Z (2009) Hypophosphatemia: the common denominator of all rickets. J Bone Miner Metab 27:392–401PubMedCrossRef

10.

Berndt TJ, Schiavi S, Kumar R (2005) “Phosphatonins” and the regulation of phosphorus homeostasis. Am J Physiol Renal Physiol 289:F1170–F1182PubMedCrossRef

11.

Alizadeh Naderi AS, Reilly RF (2010) Hereditary disorders of renal phosphate wasting. Nat Rev Nephrol 6:657–665PubMedCrossRef

12.

Farrow EG, White KE (2010) Recent advances in renal phosphate handling. Nat Rev Nephrol 6:207–217PubMedCrossRef

13.

Bergwitz C, Huppner H (2010) Regulation of phosphate homeostasis by PTH, vitamin D and FGF-23. Annu Rev Med 61:91–104PubMedCrossRef

14.

Alon US (2011) Clinical practice: Fibroblast growth factor (FGF)23: a new hormone. Eur J Pediatr 170:545–554PubMedCrossRef

15.

Xu H, Bai L, Collins JF, Ghishan FK (2002) Age-dependent regulation of rat intestinal type IIb sodium-phosphate cotransporter by 1,25-(OH)2 vitamin D3. Am J Physiol Cell Physiol 282:C487–C493PubMed

16.

Tenenhouse HS (2005) Regulation of phosphorus homeostasis by the type IIa Na/phosphate cotransporter. Annu Rev Nutr 25:197–214PubMedCrossRef

17.

Wesseling-Perry K (2010) FGF-23 in bone biology. Pediatr Nephrol 25:603–608PubMedCrossRef

18.

Xu H, Collins JF, Bai L, Kiela PR, Ghishan FK (2001) Regulation of the human sodium-phosphate cotransporter NaPi-IIb gene promoter by epidermal growth factor. Am J Physiol Cell Physiol 280:C628–C636PubMed

19.

Arima K, Hines ER, Kiela PR, Drees JB, Collins JF, Ghishan FK (2002) Glucocorticoid regulation and glycosylation of mouse intestinal type IIb Na-Pi cotransporter during ontogeny. Am J Physiol Gastrointest Liver Physiol 283:G426–G434PubMed

20.

Xu H, Uno JK, Inouye M, Xu L, Drees JB, Collins JF, Ghishan FK (2003) Regulation of intestinal NaPi-IIb cotransporter gene expression by estrogen. Am J Physiol Gastrointest Liver Physiol 285:G1317–G1324PubMed

21.

Stauber A, Radanovic T, Stange G, Murer H, Wagner CA, Biber J (2005) Regulation of intestinal phosphate transport. II. Metabolic acidosis stimulates Na+−dependent phosphate absorption and expression of the Na+−Pi cotransporter NaPi-IIb in small intestine. Am J Physiol Gastrointest Liver Physiol 288:G501–G506PubMedCrossRef

22.

Murer H, Forster I, Biber J (2004) The sodium phosphate cotransporter family SLC34. Pflügers Arch 447:763–767PubMedCrossRef

23.

Segawa H, Kaneko I, Yamanaka S, Ito M, Kuwahata M, Inoue Y, Kato S, Miyamoto K (2004) Intestinal Na-P(i) cotransporter adaptation to dietary P(i) content in vitamin D receptor null mice. Am J Physiol Renal Physiol 287:F39–F47PubMedCrossRef

24.

Capuano P, Radanovic T, Wagner CA, Bacic D, Kato S, Uchiyama Y, St Arnoud R, Murer H, Biber J (2005) Intestinal and renal adaptation to a low-Pi diet of type II NaPi cotransporters in vitamin D receptor- and 1 OHase-deficient mice. Am J Physiol Cell Physiol 288:C429–C434PubMedCrossRef

25.

Magne D, Bluteau G, Faucheux C, Palmer G, Vignes-Colombeix C, Pilet P, Rouillon T, Caverzasio J, Weiss P, Daculsi G, Guicheux J (2003) Phosphate is a specific signal for ATDC5 chondrocyte maturation and apoptosis-associated mineralization: possible implication of apoptosis in the regulation of endochondral ossification. J Bone Miner Res 18:1430–1442PubMedCrossRef

26.

Antoniucci DM, Yamashita T, Portale AA (2006) Dietary phosphorus regulates serum fibroblast growth factor-23 concentrations in healthy men. J Clin Endocrinol Metab 91:3144–3149PubMedCrossRef

27.

Bacic D, Lehir M, Biber J, Kaissling B, Murer H, Wagner CA (2006) The renal Na+/phosphate cotransporter NaPi-IIa is internalized via the receptor-mediated endocytic route in response to parathyroid hormone. Kidney Int 69:495–503PubMedCrossRef

28.

Villa-Bellosta R, Ravera S, Sorribas V, Stange G, Levi M, Murer H, Biber J, Forster IC (2009) The Na+−Pi cotransporter PiT-2 (SLC20A2) is expressed in the apical membrane of rat renal proximal tubules and regulated by dietary Pi. Am J Physiol Renal Physiol 296:F691–F699PubMedCrossRef

29.

Biber J, Hernando N, Forster I, Murer H (2009) Regulation of phosphate transport in proximal tubules. Pflügers Arch 458:39–52PubMedCrossRef

30.

Segawa H, Kaneko I, Takahashi A, Kuwahata M, Ito M, Ohkido I, Tatsumi S, Miyamoto K (2002) Growth-related renal type II Na/P i cotransporter. J Biol Chem 277:19665–19672PubMedCrossRef

31.

Prie D, Urena TP, Friedlander G (2009) Latest findings in phosphate homeostasis. Kidney Int 75:882–889PubMedCrossRef

32.

Segawa H, Yamanaka S, Ito M, Kuwahata M, Shono M, Yamamoto T, Miyamoto K (2005) Internalization of renal type IIc Na-Pi cotransporter in response to a high-phosphate diet. Am J Physiol Renal Physiol 288:F587–F596PubMedCrossRef

33.

Segawa H, Onitsuka A, Kuwahata M, Hanabusa E, Furutani J, Kaneko I, Tomoe Y, Aranami F, Matsumoto N, Ito M, Matsumoto M, Li M, Amizuka N, Miyamoto K (2009) Type IIc sodium-dependent phosphate transporter regulates calcium metabolism. J Am Soc Nephrol 20:104–113PubMedCrossRef

34.

Bergwitz C, Roslin NM, Tieder M, Loredo-Osti JC, Bastepe M, Abu-Zahra H, Frappier D, Burkett K, Carpenter TO, Anderson D, Garabedian M, Sermet I, Fujiwara TM, Morgan K, Tenenhouse HS, Juppner H (2006) SLC34A3 mutations in patients with hereditary hypophosphatemic rickets with hypercalciuria predict a key role for the sodium-phosphate cotransporter NaPi-IIc in maintaining phosphate homeostasis. Am J Hum Genet 78:179–192PubMedCrossRef

35.

Villa-Bellosta R, Sorribas V (2010) Compensatory regulation of the sodium/phosphate cotransporters NaPi-IIc (SCL34A3) and Pit-2 (SLC20A2) during Pi deprivation and acidosis. Pflügers Arch 459:499–508PubMedCrossRef

36.

Silver J, Naveh-Many T (2010) FGF-23 and the parathyroid glands. Pediatr Nephrol 25:2241–2245PubMedCrossRef

37.

Kuro-o M (2010) Overview of the FGF-23 -Klotho axis. Pediatr Nephrol 25:583–590PubMedCrossRef

38.

Liu S, Zhou J, Tang W, Jiang X, Rowe DW, Quarles LD (2006) Pathogenic role of FGF-23 in Hyp mice. Am J Physiol Endocrinol Metab 291:38–49CrossRef

39.

Kolek OI, Hines ER, Jones MD, LeSueur LK, Lipko MA, Kiela PR, Collins JF, Haussler MR, Ghishan FK (2005) 1 α,25-Dihydroxyvitamin D3 upregulates FGF-23 gene expression in bone: the final link in a renal-gastrointestinal-skeletal axis that controls phosphate transport. Am J Physiol Gastrointest Liver Physiol 289:G1036–G1042PubMedCrossRef

40.

Yoshiko Y, Wang H, Minamizaki T, Ijuin C, Yamamoto R, Suemune S, Kozai K, Tanne K, Aubin JE, Maeda N (2007) Mineralized tissue cells are a principal source of FGF-23. Bone 40:1565–1573PubMedCrossRef

41.

Shimada T, Kakitani M, Yamazaki Y, Hasegawa H, Takeuchi Y, Fujita T, Fukumoto S, Tomizuka K, Yamashita T (2004) Targeted ablation of FGF-23 demonstrates an essential physiological role of FGF-23 in phosphate and vitamin D metabolism. J Clin Invest 113:561–568PubMed

42.

Urakawa I, Yamazaki Y, Shimada T, Iijima K, Hasegawa H, Okawa K, Fujita T, Fukumoto S, Yamashita T (2006) Klotho converts canonical FGF receptor into a specific receptor for FGF-23. Nature 444:770–774PubMedCrossRef

43.

Shimada T, Yamazaki Y, Takahashi M, Hasegawa H, Urakawa I, Oshima T, Ono K, Kakitani M, Tomizuka K, Fujita T, Fukumoto S, Yamashita T (2005) Vitamin D receptor-independent FGF-23 actions in regulation phosphate and vitamin D metabolism. Am J Physiol Renal Physiol 289:F1088–F1095PubMedCrossRef

44.

Wang H, Yoshiko Y, Yamamoto R, Minamizaki T, Kozai K, Tanne K, Aubin JE, Maeda N (2008) Overexpression of fibroblast growth factor 23 suppresses osteoblast differentiation and matrix mineralization in vitro. J Bone Miner Res 23:939–948PubMedCrossRef

45.

Hunter WL, Arsenault AL, Hodsman AB (1991) Rearrangement of the metaphyseal vasculature of the rat growth plate in rickets and rachitic reversal: a model of vascular arrest and angiogenesis renewed. Anat Rec 229:453–461PubMedCrossRef

46.

Chang W, Tu C, Pratt S, Chen TH, Shoback D (2002) Extracellular Ca(2+)-sensing receptors modulate matrix production and mineralization in chondrogenic RCJ3.1C5.18 cells. Endocrinology 143:1467–1474PubMedCrossRef

47.

Sabbagh Y, Carpenter TO, Demay MB (2005) Hypophosphatemia leads to rickets by impairing caspase-mediated apoptosis of hypertrophic chondrocytes. Proc Natl Acad Sci USA 102:9637–9642PubMedCrossRef

48.

Li YC, Amling M, Pirro AE, Priemel M, Meuse J, Baron R, Delling G, Demay MB (1998) Normalization of mineral ion homeostasis by dietary means prevents hyperparathyroidism, rickets, and osteomalacia, but not alopecia in vitamin D receptor-ablated mice. Endocrinology 139:4391–4396PubMedCrossRef

49.

Dardenne O, Prud’homme J, Glorieux FH, St-Arnaud R (2007) Rescue of the phenotype of CYP27B1 (1alpha-hydroxylase)-deficient mice. J Steroid Biochem Mol Biol 89–90:327–330

50.

Miedlich SU, Zalutskaya A, Zhu ED, Demay MB (2010) Phosphate-induced apoptosis of hypertrophic chondrocytes is associated with a decrease in mitochondrial membrane potential and is dependent upon Erk1/2 phosphorylation. J Biol Chem 285:18270–18275PubMedCrossRef

Titel: Phosphate homeostasis and its role in bone health
verfasst von: Maria Goretti M. G. Penido
Uri S. Alon
Publikationsdatum: 01.11.2012
Verlag: Springer-Verlag
Erschienen in: Pediatric Nephrology / Ausgabe 11/2012
Print ISSN: 0931-041X
Elektronische ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-012-2175-z

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