1α,25-dihydroxyvitamin D3 acts predominately in mature osteoblasts under conditions of high extracellular phosphate to increase fibroblast growth factor 23 production in vitro

Osteoblasts/osteocytes are the principle sources of fibroblast growth factor 23 (FGF23), a phosphaturic hormone, but the regulation of FGF23 expression during osteoblast development remains uncertain. Because 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) and inorganic phosphate (Pi) may act as potent activators of FGF23 expression, we estimated how these molecules regulate FGF23 expression during rat osteoblast development in vitro. 1,25(OH)2D3-dependent FGF23 production was restricted largely to mature cells in correlation with increased vitamin D receptor (VDR) mRNA levels, in particular, when Pi was present. Pi alone and more so in combination with 1,25(OH)2D3 increased FGF23 production and VDR mRNA expression. Parathyroid hormone, stanniocalcin 1, prostaglandin E2, FGF2, and foscarnet did not increase FGF23 mRNA expression. Thus, these results suggest that 1,25(OH)2D3 may exert its largest effect on FGF23 expression/production when exposed to high levels of extracellular Pi in osteoblasts/osteocytes.

[1]  R. Kaneko,et al.  Effects of transgenic Pit-1 overexpression on calcium phosphate and bone metabolism , 2010, Journal of Bone and Mineral Metabolism.

[2]  D. Goltzman,et al.  Bone formation regulates circulating concentrations of fibroblast growth factor 23. , 2009, Endocrinology.

[3]  Hang Lee,et al.  Effects of hPTH(1‐34) Infusion on Circulating Serum Phosphate, 1,25‐Dihydroxyvitamin D, and FGF23 Levels in Healthy Men , 2009, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[4]  Zhousheng Xiao,et al.  Novel regulators of Fgf23 expression and mineralization in Hyp bone. , 2009, Molecular endocrinology.

[5]  M. Razzaque,et al.  Reversal of mineral ion homeostasis and soft-tissue calcification of klotho knockout mice by deletion of vitamin D 1alpha-hydroxylase. , 2009, Kidney international.

[6]  K. Takano,et al.  PTH(7-84) inhibits PTH(1-34)-induced 1,25-(OH)2D3 production in murine renal tubules. , 2009, Biochemical and biophysical research communications.

[7]  J. Pelletier,et al.  Differential modulation of RANKL isoforms by human osteoarthritic subchondral bone osteoblasts: influence of osteotropic factors. , 2008, Bone.

[8]  Jian Q. Feng,et al.  Pathogenic role of Fgf23 in Dmp1-null mice. , 2008, American journal of physiology. Endocrinology and metabolism.

[9]  J. Aubin,et al.  Overexpression of Fibroblast Growth Factor 23 Suppresses Osteoblast Differentiation and Matrix Mineralization In Vitro , 2008, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[10]  M. Mohammadi,et al.  The parathyroid is a target organ for FGF23 in rats. , 2007, The Journal of clinical investigation.

[11]  R. D'Souza,et al.  Dentin Matrix Protein 1 (DMP1): New and Important Roles for Biomineralization and Phosphate Homeostasis , 2007, Journal of dental research.

[12]  A. Arnold,et al.  Parathyroid hormone regulates fibroblast growth factor-23 in a mouse model of primary hyperparathyroidism. , 2007, Journal of the American Society of Nephrology : JASN.

[13]  S. Kliewer,et al.  Tissue-specific Expression of βKlotho and Fibroblast Growth Factor (FGF) Receptor Isoforms Determines Metabolic Activity of FGF19 and FGF21* , 2007, Journal of Biological Chemistry.

[14]  J. Aubin,et al.  Mineralized tissue cells are a principal source of FGF23. , 2007, Bone.

[15]  L. Quarles,et al.  How fibroblast growth factor 23 works. , 2007, Journal of the American Society of Nephrology : JASN.

[16]  J. Aubin,et al.  Osteoblast Autonomous Pi Regulation via Pit1 Plays a Role in Bone Mineralization , 2007, Molecular and Cellular Biology.

[17]  M. Haussler,et al.  1,25-Dihydroxyvitamin D3/VDR-mediated induction of FGF23 as well as transcriptional control of other bone anabolic and catabolic genes that orchestrate the regulation of phosphate and calcium mineral metabolism , 2007, The Journal of Steroid Biochemistry and Molecular Biology.

[18]  K. Okawa,et al.  Klotho converts canonical FGF receptor into a specific receptor for FGF23 , 2006, Nature.

[19]  M. Razzaque,et al.  Genetic ablation of vitamin D activation pathway reverses biochemical and skeletal anomalies in Fgf-23-null animals. , 2006, American Journal of Pathology.

[20]  L. Bonewald,et al.  Loss of DMP1 causes rickets and osteomalacia and identifies a role for osteocytes in mineral metabolism , 2006, Nature Genetics.

[21]  Xi Jiang,et al.  Pathogenic role of Fgf23 in Hyp mice. , 2006, American journal of physiology. Endocrinology and metabolism.

[22]  Jason R. Stubbs,et al.  Fibroblast growth factor 23 is a counter-regulatory phosphaturic hormone for vitamin D. , 2006, Journal of the American Society of Nephrology : JASN.

[23]  Y. Oiso,et al.  Enhanced Expression of the Inorganic Phosphate Transporter Pit‐1 Is Involved in BMP‐2–Induced Matrix Mineralization in Osteoblast‐Like Cells , 2006, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[24]  Y. Yoshiko,et al.  Stanniocalcin 1 Acts as a Paracrine Regulator of Growth Plate Chondrogenesis* , 2006, Journal of Biological Chemistry.

[25]  M. Haussler,et al.  1alpha,25-Dihydroxyvitamin D3 upregulates FGF23 gene expression in bone: the final link in a renal-gastrointestinal-skeletal axis that controls phosphate transport. , 2005, American journal of physiology. Gastrointestinal and liver physiology.

[26]  B. Lanske,et al.  Overexpression of Human PHEX Under the Human β‐Actin Promoter Does Not Fully Rescue the Hyp Mouse Phenotype , 2005, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[27]  K. White,et al.  Genetic dissection of phosphate- and vitamin D-mediated regulation of circulating Fgf23 concentrations. , 2005, Bone.

[28]  K. White,et al.  FGF23 and disorders of phosphate homeostasis. , 2005, Cytokine & growth factor reviews.

[29]  S. Kato,et al.  Circulating FGF-23 Is Regulated by 1α,25-Dihydroxyvitamin D3 and Phosphorus in Vivo* , 2005, Journal of Biological Chemistry.

[30]  K. Miyamoto,et al.  Vitamin D and phosphate regulate fibroblast growth factor-23 in K-562 cells. , 2005, American journal of physiology. Endocrinology and metabolism.

[31]  M. Somerman,et al.  FGF2 Alters Expression of the Pyrophosphate/Phosphate Regulating Proteins, PC-1, ANK and TNAP, in the Calvarial Osteoblastic Cell Line, MC3T3E1(C4) , 2005, Connective tissue research.

[32]  R. Mason,et al.  Bone as a source of FGF23: regulation by phosphate? , 2004, Bone.

[33]  Xi Jiang,et al.  Dentin matrix protein 1 expression during osteoblastic differentiation, generation of an osteocyte GFP-transgene. , 2004, Bone.

[34]  C. Ohlsson,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. , 2004, Endocrinology.

[35]  K. Kamiya,et al.  Sinoatrial Node Dysfunction and Early Unexpected Death of Mice With a Defect of klotho Gene Expression , 2004, Circulation.

[36]  Y. Takeuchi,et al.  FGF‐23 Is a Potent Regulator of Vitamin D Metabolism and Phosphate Homeostasis , 2003, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[37]  G. Beck.  Inorganic phosphate as a signaling molecule in osteoblast differentiation , 2003, Journal of cellular biochemistry.

[38]  J. Aubin,et al.  Stanniocalcin 1 stimulates osteoblast differentiation in rat calvaria cell cultures. , 2003, Endocrinology.

[39]  K. White,et al.  FGF-23 in fibrous dysplasia of bone and its relationship to renal phosphate wasting. , 2003, The Journal of clinical investigation.

[40]  L. Quarles,et al.  FGF23, PHEX, and MEPE regulation of phosphate homeostasis and skeletal mineralization. , 2003, American journal of physiology. Endocrinology and metabolism.

[41]  R. Kumar,et al.  Modulation of growth factor/cytokine synthesis and signaling by 1alpha,25-dihydroxyvitamin D(3): implications in cell growth and differentiation. , 2002, Endocrine reviews.

[42]  Y. Nabeshima,et al.  Mediation of Unusually High Concentrations of 1,25-Dihydroxyvitamin D in Homozygous klotho Mutant Mice by Increased Expression of Renal 1α-Hydroxylase Gene. , 2002, Endocrinology.

[43]  T. Komori,et al.  Dentin Matrix Protein 1 Is Predominantly Expressed in Chicken and Rat Osteocytes But Not in Osteoblasts , 2001, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[44]  G. FitzGerald,et al.  Genetic and pharmacological analysis of prostanoid receptor function. , 2001, The Journal of clinical investigation.

[45]  T. Meitinger,et al.  Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23 , 2000, Nature Genetics.

[46]  S. Narumiya,et al.  The role of prostaglandin E receptor subtypes (EP1, EP2, EP3, and EP4) in bone resorption: an analysis using specific agonists for the respective EPs. , 2000, Endocrinology.

[47]  M. Kuro-o,et al.  Independent impairment of osteoblast and osteoclast differentiation in klotho mouse exhibiting low-turnover osteopenia. , 1999, The Journal of clinical investigation.

[48]  B. Kaissling,et al.  Renal brush border membrane Na/Pi-cotransport: molecular aspects in PTH-dependent and dietary regulation. , 1996, Kidney international.

[49]  J. Aubin,et al.  Inorganic phosphate added exogenously or released from beta-glycerophosphate initiates mineralization of osteoid nodules in vitro. , 1992, Bone and mineral.

[50]  T. Dousa,et al.  Quantitation of the Na(+)-Pi cotransporter in renal cortical brush border membranes. [14C]phosphonoformic acid as a useful probe to determine the density and its change in response to parathyroid hormone. , 1991, The Journal of biological chemistry.

[51]  E. Brown,et al.  Primary hyperparathyroidism with low serum 1,25-dihydroxyvitamin D levels. , 1986, The Journal of clinical endocrinology and metabolism.

[52]  J. Aubin,et al.  Mineralized bone nodules formedin vitro from enzymatically released rat calvaria cell populations , 1986, Calcified Tissue International.

[53]  C. Schmid,et al.  Prostaglandin E2 Stimulates Sodium-Dependent Phosphate Transport in Osteoblastic Cells via a Protein Kinase C-Mediated Pathway. , 1998, Endocrinology.

[54]  J. Bonjour,et al.  Regulation of Na-dependent Pi transport by parathyroid hormone in osteoblast-like cells. , 1989, The American journal of physiology.