Skip to main content

Advertisement

SpringerLink
Log in

Sclerostin Directly Stimulates Osteocyte Synthesis of Fibroblast Growth Factor-23

  • Original Research
  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Abstract

Osteocyte produced fibroblast growth factor 23 (FGF23) is the key regulator of serum phosphate (Pi) homeostasis. The interplay between parathyroid hormone (PTH), FGF23 and other proteins that regulate FGF23 production and serum Pi levels is complex and incompletely characterised. Evidence suggests that the protein product of the SOST gene, sclerostin (SCL), also a PTH target and also produced by osteocytes, plays a role in FGF23 expression, however the mechanism for this effect is unclear. Part of the problem of understanding the interplay of these mediators is the complex multi-organ system that achieves Pi homeostasis in vivo. In the current study, we sought to address this using a cell line model of the osteocyte, IDG-SW3, known to express FGF23 at both the mRNA and protein levels. In cultures of differentiated IDG-SW3 cells, both PTH1-34 and recombinant human (rh) SCL remarkably induced Fgf23 mRNA expression dose-dependently within 3 h. Both rhPTH1-34 and rhSCL also strongly induced C-terminal FGF23 protein secretion. Secreted intact FGF23 levels remained unchanged, consistent with constitutive post-translational cleavage of FGF23 in this cell model. Both rhPTH1-34 and rhSCL treatments significantly suppressed mRNA levels of Phex, Dmp1 and Enpp1 mRNA, encoding putative negative regulators of FGF23 levels, and induced Galnt3 mRNA expression, encoding N-acetylgalactosaminyl-transferase 3 (GalNAc-T3), which protects FGF23 from furin-like proprotein convertase-mediated cleavage. The effect of both rhPTH1-34 and rhSCL was antagonised by pre-treatment with the NF-κβ signalling inhibitors, BAY11 and TPCK. RhSCL also stimulated FGF23 mRNA expression in ex vivo cultures of human bone. These findings provide evidence for the direct regulation of FGF23 expression by sclerostin. Locally expressed sclerostin via the induction of FGF23 in osteocytes thus has the potential to contribute to the regulation of Pi homeostasis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. ADHR Consortium (2000) Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23. Nat Genet 26:345–348

    Article  Google Scholar 

  2. Shimada T, Mizutani S, Muto T, Yoneya T, Hino R, Takeda S, Takeuchi Y, Fujita T, Fukumoto S, Yamashita T (2001) Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia. Proc Natl Acad Sci USA 98:6500–6505

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. 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 FGF23. Nature 444:770–774

    Article  CAS  PubMed  Google Scholar 

  4. Kurosu H, Ogawa Y, Miyoshi M, Yamamoto M, Nandi A, Rosenblatt KP, Baum MG, Schiavi S, Hu MC, Moe OW, Kuro-o M (2006) Regulation of fibroblast growth factor-23 signaling by klotho. J Biol Chem 281:6120–6123

    Article  CAS  PubMed  Google Scholar 

  5. Ito N, Findlay DM, Atkins GJ (2014) Osteocyte communication with the kidney via the production of FGF23: remote control of phosphate homeostasis. Clin Rev Bone Miner Metab 12:44–58

    Article  CAS  Google Scholar 

  6. Perwad F, Azam N, Zhang MY, Yamashita T, Tenenhouse HS, Portale AA (2005) Dietary and serum phosphorus regulate fibroblast growth factor 23 expression and 1,25-dihydroxyvitamin D metabolism in mice. Endocrinology 146:5358–5364

    Article  CAS  PubMed  Google Scholar 

  7. Saito H, Maeda A, Ohtomo S, Hirata M, Kusano K, Kato S, Ogata E, Segawa H, Miyamoto K, Fukushima N (2005) Circulating FGF-23 is regulated by 1alpha,25-dihydroxyvitamin D3 and phosphorus in vivo. J Biol Chem 280:2543–2549

    Article  CAS  PubMed  Google Scholar 

  8. Ferrari SL, Bonjour JP, Rizzoli R (2005) Fibroblast growth factor-23 relationship to dietary phosphate and renal phosphate handling in healthy young men. J Clin Endocrinol Metab 90:1519–1524

    Article  CAS  PubMed  Google Scholar 

  9. Yu X, Sabbagh Y, Davis SI, Demay MB, White KE (2005) Genetic dissection of phosphate- and vitamin D-mediated regulation of circulating Fgf23 concentrations. Bone 36:971–977

    Article  CAS  PubMed  Google Scholar 

  10. Burnett SM, Gunawardene SC, Bringhurst FR, Juppner H, Lee H, Finkelstein JS (2006) Regulation of C-terminal and intact FGF-23 by dietary phosphate in men and women. J Bone Miner Res 21:1187–1196

    Article  CAS  PubMed  Google Scholar 

  11. Yamamoto R, Minamizaki T, Yoshiko Y, Yoshioka H, Tanne K, Aubin JE, Maeda N (2010) 1alpha,25-dihydroxyvitamin D3 acts predominately in mature osteoblasts under conditions of high extracellular phosphate to increase fibroblast growth factor 23 production in vitro. J Endocrinol 206:279–286

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Ito N, Findlay DM, Anderson PH, Bonewald LF, Atkins GJ (2013) Extracellular phosphate modulates the effect of 1alpha,25-dihydroxy vitamin D3 (1,25D) on osteocyte like cells. J Steroid Biochem Mol Biol 136:183–186

    Article  CAS  PubMed  Google Scholar 

  13. Takashi Y, Kosako H, Sawatsubashi S, Kinoshita Y, Ito N, Tsoumpra MK, Nangaku M, Abe M, Matsuhisa M, Kato S, Matsumoto T, Fukumoto S (2019) Activation of unliganded FGF receptor by extracellular phosphate potentiates proteolytic protection of FGF23 by its O-glycosylation. Proc Natl Acad Sci USA 116:11418–11427

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Levi M, Gratton E (2019) Visualizing the regulation of SLC34 proteins at the apical membrane. Pflugers Arch 471:533–542

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Gattineni J, Bates C, Twombley K, Dwarakanath V, Robinson ML, Goetz R, Mohammadi M, Baum M (2009) FGF23 decreases renal NaPi-2a and NaPi-2c expression and induces hypophosphatemia in vivo predominantly via FGF receptor 1. Am J Physiol Renal Physiol 297:F282-291

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Zierold C, Mings JA, DeLuca HF (2001) Parathyroid hormone regulates 25-hydroxyvitamin D(3)-24-hydroxylase mRNA by altering its stability. Proc Natl Acad Sci USA 98:13572–13576

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Zierold C, Mings JA, DeLuca HF (2003) Regulation of 25-hydroxyvitamin D3–24-hydroxylase mRNA by 1,25-dihydroxyvitamin D3 and parathyroid hormone. J Cell Biochem 88:234–237

    Article  CAS  PubMed  Google Scholar 

  18. Shimada T, Hasegawa H, Yamazaki Y, Muto T, Hino R, Takeuchi Y, Fujita T, Nakahara K, Fukumoto S, Yamashita T (2004) FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis. J Bone Miner Res 19:429–435

    Article  CAS  PubMed  Google Scholar 

  19. Lavi-Moshayoff V, Wasserman G, Meir T, Silver J, Naveh-Many T (2010) PTH increases FGF23 gene expression and mediates the high-FGF23 levels of experimental kidney failure: a bone parathyroid feedback loop. Am J Physiol Renal Physiol 299:F882-889

    Article  CAS  PubMed  Google Scholar 

  20. Rhee Y, Bivi N, Farrow E, Lezcano V, Plotkin LI, White KE, Bellido T (2011) Parathyroid hormone receptor signaling in osteocytes increases the expression of fibroblast growth factor-23 in vitro and in vivo. Bone 49:636–643

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Topaz O, Shurman DL, Bergman R, Indelman M, Ratajczak P, Mizrachi M, Khamaysi Z, Behar D, Petronius D, Friedman V, Zelikovic I, Raimer S, Metzker A, Richard G, Sprecher E (2004) Mutations in GALNT3, encoding a protein involved in O-linked glycosylation, cause familial tumoral calcinosis. Nat Genet 36:579–581

    Article  CAS  PubMed  Google Scholar 

  22. Frishberg Y, Ito N, Rinat C, Yamazaki Y, Feinstein S, Urakawa I, Navon-Elkan P, Becker-Cohen R, Yamashita T, Araya K, Igarashi T, Fujita T, Fukumoto S (2007) Hyperostosis-hyperphosphatemia syndrome: a congenital disorder of O-glycosylation associated with augmented processing of fibroblast growth factor 23. J Bone Miner Res 22:235–242

    Article  CAS  PubMed  Google Scholar 

  23. Ichikawa S, Sorenson AH, Austin AM, Mackenzie DS, Fritz TA, Moh A, Hui SL, Econs MJ (2009) Ablation of the Galnt3 gene leads to low-circulating intact fibroblast growth factor 23 (Fgf23) concentrations and hyperphosphatemia despite increased Fgf23 expression. Endocrinology 150:2543–2550

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Bellido T, Ali AA, Gubrij I, Plotkin LI, Fu Q, O’Brien CA, Manolagas SC, Jilka RL (2005) Chronic elevation of parathyroid hormone in mice reduces expression of sclerostin by osteocytes: a novel mechanism for hormonal control of osteoblastogenesis. Endocrinology 146:4577–4583

    Article  CAS  PubMed  Google Scholar 

  25. Keller H, Kneissel M (2005) SOST is a target gene for PTH in bone. Bone 37:148–158

    Article  CAS  PubMed  Google Scholar 

  26. Brunkow ME, Gardner JC, Van Ness J, Paeper BW, Kovacevich BR, Proll S, Skonier JE, Zhao L, Sabo PJ, Fu Y, Alisch RS, Gillett L, Colbert T, Tacconi P, Galas D, Hamersma H, Beighton P, Mulligan J (2001) Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein. Am J Hum Genet 68:577–589

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Poole KE, van Bezooijen RL, Loveridge N, Hamersma H, Papapoulos SE, Löwik CW, Reeve J (2005) Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation. FASEB J 19:1842–1844

    Article  CAS  PubMed  Google Scholar 

  28. Atkins GJ, Rowe PS, Lim HP, Welldon KJ, Ormsby R, Wijenayaka AR, Zelenchuk L, Evdokiou A, Findlay DM (2011) Sclerostin is a locally acting regulator of late-osteoblast/preosteocyte differentiation and regulates mineralization through a MEPE-ASARM-dependent mechanism. J Bone Miner Res 26:1425–1436

    Article  CAS  PubMed  Google Scholar 

  29. Kogawa M, Wijenayaka AR, Ormsby RT, Thomas GP, Anderson PH, Bonewald LF, Findlay DM, Atkins GJ (2013) Sclerostin regulates release of bone mineral by osteocytes by induction of carbonic anhydrase 2. J Bone Miner Res 28:2436–2448

    Article  CAS  PubMed  Google Scholar 

  30. Wijenayaka AR, Kogawa M, Lim HP, Bonewald LF, Findlay DM, Atkins GJ (2011) Sclerostin stimulates osteocyte support of osteoclast activity by a RANKL-dependent pathway. PLoS ONE 6:e25900

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Li X, Zhang Y, Kang H, Liu W, Liu P, Zhang J, Harris SE, Wu D (2005) Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J Biol Chem 280:19883–19887

    Article  CAS  PubMed  Google Scholar 

  32. Ren Y, Han X, Jing Y, Yuan B, Ke H, Liu M, Feng JQ (2016) Sclerostin antibody (Scl-Ab) improves osteomalacia phenotype in dentin matrix protein 1(Dmp1) knockout mice with little impact on serum levels of phosphorus and FGF23. Matrix Biol 52–54:151–161

    Article  PubMed  Google Scholar 

  33. Ryan ZC, Ketha H, McNulty MS, McGee-Lawrence M, Craig TA, Grande JP, Westendorf JJ, Singh RJ, Kumar R (2013) Sclerostin alters serum vitamin D metabolite and fibroblast growth factor 23 concentrations and the urinary excretion of calcium. Proc Natl Acad Sci USA 110:6199–6204

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Liu S, Tang W, Fang J, Ren J, Li H, Xiao Z, Quarles LD (2009) Novel regulators of Fgf23 expression and mineralization in Hyp bone. Mol Endocrinol 23:1505–1518

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Kolek OI, Hines ER, Jones MD, LeSueur LK, Lipko MA, Kiela PR, Collins JF, Haussler MR, Ghishan FK (2005) 1alpha,25-Dihydroxyvitamin D3 upregulates FGF23 gene expression in bone: the final link in a renal-gastrointestinal-skeletal axis that controls phosphate transport. Am J Physiol Gastrointest Liver Physiol 289:G1036-1042

    Article  CAS  PubMed  Google Scholar 

  36. Woo SM, Rosser J, Dusevich V, Kalajzic I, Bonewald LF (2011) Cell line IDG-SW3 replicates osteoblast-to-late-osteocyte differentiation in vitro and accelerates bone formation in vivo. J Bone Miner Res 26:2634–2646

    Article  CAS  PubMed  Google Scholar 

  37. Ito N, Wijenayaka AR, Prideaux M, Kogawa M, Ormsby RT, Evdokiou A, Bonewald LF, Findlay DM, Atkins GJ (2015) Regulation of FGF23 expression in IDG-SW3 osteocytes and human bone by pro-inflammatory stimuli. Mol Cell Endocrinol 399:208–218

    Article  CAS  PubMed  Google Scholar 

  38. Prideaux M, Schutz C, Wijenayaka AR, Findlay DM, Campbell DG, Solomon LB, Atkins GJ (2016) Isolation of osteocytes from human trabecular bone. Bone 88:64–72

    Article  CAS  PubMed  Google Scholar 

  39. Ito N, Fukumoto S, Takeuchi Y, Yasuda T, Hasegawa Y, Takemoto F, Tajima T, Dobashi K, Yamazaki Y, Yamashita T, Fujita T (2005) Comparison of two assays for fibroblast growth factor (FGF)-23. J Bone Miner Metab 23:435–440

    Article  CAS  PubMed  Google Scholar 

  40. Feyen JH, Elford P, Di Padova FE, Trechsel U (1989) Interleukin-6 is produced by bone and modulated by parathyroid hormone. J Bone Miner Res 4:633–638

    Article  CAS  PubMed  Google Scholar 

  41. Lowik CW, van der Pluijm G, Bloys H, Hoekman K, Bijvoet OL, Aarden LA, Papapoulos SE (1989) Parathyroid hormone (PTH) and PTH-like protein (PLP) stimulate interleukin-6 production by osteogenic cells: a possible role of interleukin-6 in osteoclastogenesis. Biochem Biophys Res Commun 162:1546–1552

    Article  CAS  PubMed  Google Scholar 

  42. Guo Y, Yuan W, Wang L, Shang M, Peng Y (2011) Parathyroid hormone-potentiated connective tissue growth factor expression in human renal proximal tubular cells through activating the MAPK and NF-kappaB signalling pathways. Nephrol Dial Transpl 26:839–847

    Article  CAS  Google Scholar 

  43. Burnett-Bowie SM, Henao MP, Dere ME, Lee H, Leder BZ (2009) Effects of hPTH(1–34) infusion on circulating serum phosphate, 1,25-dihydroxyvitamin D, and FGF23 levels in healthy men. J Bone Miner Res 24:1681–1685

    Article  PubMed  PubMed Central  Google Scholar 

  44. Brown WW, Juppner H, Langman CB, Price H, Farrow EG, White KE, McCormick KL (2009) Hypophosphatemia with elevations in serum fibroblast growth factor 23 in a child with Jansen’s metaphyseal chondrodysplasia. J Clin Endocrinol Metab 94:17–20

    Article  CAS  PubMed  Google Scholar 

  45. Kogawa M, Khalid KA, Wijenayaka AR, Ormsby RT, Evdokiou A, Anderson PH, Findlay DM, Atkins GJ (2018) Recombinant sclerostin antagonizes effects of ex vivo mechanical loading in trabecular bone and increases osteocyte lacunar size. Am J Physiol Cell Physiol 314:C53–C61

    Article  CAS  PubMed  Google Scholar 

  46. Prideaux M, Wijenayaka AR, Kumarasinghe DD, Ormsby RT, Evdokiou A, Findlay DM, Atkins GJ (2014) SaOS2 Osteosarcoma cells as an in vitro model for studying the transition of human osteoblasts to osteocytes. Calcif Tissue Int 95:183–193

    Article  CAS  PubMed  Google Scholar 

  47. The HYP Consortium (1995) A gene (PEX) with homologies to endopeptidases is mutated in patients with X-linked hypophosphatemic rickets. HYP Consortium Nat Genet 11:130–136

    Article  Google Scholar 

  48. Yamazaki Y, Okazaki R, Shibata M, Hasegawa Y, Satoh K, Tajima T, Takeuchi Y, Fujita T, Nakahara K, Yamashita T, Fukumoto S (2002) Increased circulatory level of biologically active full-length FGF-23 in patients with hypophosphatemic rickets/osteomalacia. J Clin Endocrinol Metab 87:4957–4960

    Article  CAS  PubMed  Google Scholar 

  49. Lorenz-Depiereux B, Bastepe M, Benet-Pages A, Amyere M, Wagenstaller J, Muller-Barth U, Badenhoop K, Kaiser SM, Rittmaster RS, Shlossberg AH, Olivares JL, Loris C, Ramos FJ, Glorieux F, Vikkula M, Juppner H, Strom TM (2006) DMP1 mutations in autosomal recessive hypophosphatemia implicate a bone matrix protein in the regulation of phosphate homeostasis. Nat Genet 38:1248–1250

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Feng JQ, Ward LM, Liu S, Lu Y, Xie Y, Yuan B, Yu X, Rauch F, Davis SI, Zhang S, Rios H, Drezner MK, Quarles LD, Bonewald LF, White KE (2006) Loss of DMP1 causes rickets and osteomalacia and identifies a role for osteocytes in mineral metabolism. Nat Genet 38:1310–1315

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Lorenz-Depiereux B, Schnabel D, Tiosano D, Hausler G, Strom TM (2010) Loss-of-function ENPP1 mutations cause both generalized arterial calcification of infancy and autosomal-recessive hypophosphatemic rickets. Am J Hum Genet 86:267–272

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Levy-Litan V, Hershkovitz E, Avizov L, Leventhal N, Bercovich D, Chalifa-Caspi V, Manor E, Buriakovsky S, Hadad Y, Goding J, Parvari R (2010) Autosomal-recessive hypophosphatemic rickets is associated with an inactivation mutation in the ENPP1 gene. Am J Hum Genet 86:273–278

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Suva LJ, Friedman PA (2020) PTH and PTHrP actions on bone. Handb Exp Pharmacol 262:27–45

    Article  PubMed  Google Scholar 

  54. Ali NN, Gilston V, Winyard PG (1999) Activation of NF-κB in human osteoblasts by stimulators of bone resorption. FEBS Lett 460:315–320

    Article  CAS  PubMed  Google Scholar 

  55. Libermann TA, Baltimore D (1990) Activation of interleukin-6 gene expression through the NF-kappa B transcription factor. Mol Cell Biol 10:2327–2334

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Guillén C, Martı́nez P, de Gortázar AR, Martı́nez MaE, Esbrit P (2002) Both N- and C-terminal domains of parathyroid hormone-related protein increase interleukin-6 by nuclear factor-κB activation in osteoblastic cells. J Biol Chem 277:28109–28117

    Article  PubMed  Google Scholar 

  57. Ewendt F, Föller M (2019) p38MAPK controls fibroblast growth factor 23 (FGF23) synthesis in UMR106-osteoblast-like cells and in IDG-SW3 osteocytes. J Endocrinol Invest 42:1477–1483

    Article  CAS  PubMed  Google Scholar 

  58. Bär L, Hase P, Föller M (2019) PKC regulates the production of fibroblast growth factor 23 (FGF23). PLoS ONE 14:e0211309

    Article  PubMed  PubMed Central  Google Scholar 

  59. Kato K, Jeanneau C, Tarp MA, Benet-Pages A, Lorenz-Depiereux B, Bennett EP, Mandel U, Strom TM, Clausen H (2006) Polypeptide GalNAc-transferase T3 and familial tumoral calcinosis. Secretion of fibroblast growth factor 23 requires O-glycosylation. J Biol Chem 281:18370–18377

    Article  CAS  PubMed  Google Scholar 

  60. Farrow EG, Yu X, Summers LJ, Davis SI, Fleet JC, Allen MR, Robling AG, Stayrook KR, Jideonwo V, Magers MJ, Garringer HJ, Vidal R, Chan RJ, Goodwin CB, Hui SL, Peacock M, White KE (2011) Iron deficiency drives an autosomal dominant hypophosphatemic rickets (ADHR) phenotype in fibroblast growth factor-23 (Fgf23) knock-in mice. Proc Natl Acad Sci USA 108:E1146-1155

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Imel EA, Peacock M, Gray AK, Padgett LR, Hui SL, Econs MJ (2011) Iron modifies plasma FGF23 differently in autosomal dominant hypophosphatemic rickets and healthy humans. J Clin Endocrinol Metab 96:3541–3549

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Schjoldager KT, Vester-Christensen MB, Goth CK, Petersen TN, Brunak S, Bennett EP, Levery SB, Clausen H (2011) A systematic study of site-specific GalNAc-type O-glycosylation modulating proprotein convertase processing. J Biol Chem 286:40122–40132

    Article  CAS  PubMed  Google Scholar 

  63. Bhattacharyya N, Wiench M, Dumitrescu C, Connolly BM, Bugge TH, Patel HV, Gafni RI, Cherman N, Cho M, Hager GL, Collins MT (2012) Mechanism of FGF23 processing in fibrous dysplasia. J Bone Miner Res 27:1132–1141

    Article  CAS  PubMed  Google Scholar 

  64. Knab VM, Corbin B, Andrukhova O, Hum JM, Ni P, Rabadi S, Maeda A, White KE, Erben RG, Juppner H, Christov M (2017) Acute parathyroid hormone injection increases C-terminal but not intact fibroblast growth factor 23 levels. Endocrinology 158:1130–1139

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Arnett TR (2010) Acidosis, hypoxia and bone. Arch Biochem Biophys 503:103–109

    Article  CAS  PubMed  Google Scholar 

  66. Tokarz D, Martins JS, Petit ET, Lin CP, Demay MB, Liu ES (2018) Hormonal regulation of osteocyte perilacunar and canalicular remodeling in the hyp mouse model of X-linked hypophosphatemia. J Bone Miner Res 33:499–509

    Article  CAS  PubMed  Google Scholar 

  67. Qin L, Raggatt LJ, Partridge NC (2004) Parathyroid hormone: a double-edged sword for bone metabolism. Trends Endocrinol Metab 15:60–65

    Article  CAS  PubMed  Google Scholar 

  68. Gupta A, Winer K, Econs MJ, Marx SJ, Collins MT (2004) FGF-23 is elevated by chronic hyperphosphatemia. J Clin Endocrinol Metab 89:4489–4492

    Article  CAS  PubMed  Google Scholar 

  69. Palomo T, Glorieux FH, Rauch F (2014) Circulating sclerostin in children and young adults with heritable bone disorders. J Clin Endocrinol Metab 99:E920-925

    Article  CAS  PubMed  Google Scholar 

  70. Kinoshita Y, Fukumoto S (2018) X-linked hypophosphatemia and FGF23-related hypophosphatemic diseases: prospect for new treatment. Endocr Rev 39:274–291

    Article  PubMed  Google Scholar 

  71. Agoro R, Ni P, Noonan ML, White KE (2020) Osteocytic FGF23 and Its Kidney Function. Front Endocrinol 11:592

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported by funding from the National Health and Medical Research Council of Australia (NHMRC) Project Grant Scheme (Grant ID 10477960).

Author information

Authors and Affiliations

  1. Biomedical Orthopaedic Research Group, Centre for Orthopaedic & Trauma Research, The University of Adelaide, Adelaide, SA, 5000, Australia

    Nobuaki Ito, Matthew Prideaux, Asiri R. Wijenayaka, Dongqing Yang, Renee T. Ormsby & Gerald J. Atkins

  2. Division of Nephrology and Endocrinology, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

    Nobuaki Ito

  3. School of Medicine, Indiana Center for Musculoskeletal Health, Indiana University, Indianapolis, IN, 46202, USA

    Matthew Prideaux & Lynda F. Bonewald

  4. Brigham and Women’s Hospital, Boston, MA, USA

    Renee T. Ormsby

Authors
  1. Nobuaki Ito
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Matthew Prideaux
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Asiri R. Wijenayaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dongqing Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Renee T. Ormsby
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lynda F. Bonewald
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Gerald J. Atkins
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gerald J. Atkins.

Ethics declarations

Conflict of interest

Nobuaki Ito, Matthew Prideaux, Asiri R. Wijenayaka, Dongqing Yang, Renee T. Ormsby, Lynda F. Bonewald and Gerald J. Atkins declared no conflicts of interest.

Human and Animal Rights and Informed Consent

Informed consent was obtained from all individual participants included in the study. The study was approved by the Human Research Ethics Committee of the RAH (Protocol no 140216a).

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PPTX 199 kb)

Supplementary file2 (DOCX 14 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ito, N., Prideaux, M., Wijenayaka, A.R. et al. Sclerostin Directly Stimulates Osteocyte Synthesis of Fibroblast Growth Factor-23. Calcif Tissue Int 109, 66–76 (2021). https://doi.org/10.1007/s00223-021-00823-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00223-021-00823-6

Keywords

Search

Navigation