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Published in: Calcified Tissue International 6/2013

01-12-2013 | Original Research

FGF23 Affects the Lineage Fate Determination of Mesenchymal Stem Cells

Authors: Yan Li, Xu He, Hannes Olauson, Tobias E. Larsson, Urban Lindgren

Published in: Calcified Tissue International | Issue 6/2013

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Abstract

FGF23 is a bone-derived hormone that regulates mineral metabolism by inhibiting renal tubular phosphate reabsorption and suppressing circulating 1,25(OH)2D and PTH levels. These effects are mediated by FGF-receptor binding and activation in the presence of its coreceptor Klotho, which is expressed in the distal tubules of the kidney. Recently, expression of Klotho in skeletal tissues has been reported, indicating a direct, yet unclear, extrarenal effect of FGF23 on cells involved with bone development and remodeling. In the present study, we found that bone marrow stromal cells harvested from Klotho null mice developed fewer osteoblastic but more adipocytic colonies than cells from wild-type mice. The underlying mechanism was explored by experiments on mouse C3H10T1/2 cells. We found that Klotho was weakly expressed and that FGF23 dose-dependently affected the lineage fate determination. The effects of FGF23 on cell differentiation can be diminished by SU 5402, a specific tyrosine kinase inhibitor for FGF receptors. Our results indicate that FGF23 directly affects the differentiation of bone marrow stromal cells.
Literature
1.
go back to reference Ubaidus S, Li M, Sultana S, de Freitas PH, Oda K, Maeda T, Takagi R, Amizuka N (2009) FGF23 is mainly synthesized by osteocytes in the regularly distributed osteocytic lacunar canalicular system established after physiological bone remodeling. J Electron Microsc (Tokyo) 58:381–392CrossRef Ubaidus S, Li M, Sultana S, de Freitas PH, Oda K, Maeda T, Takagi R, Amizuka N (2009) FGF23 is mainly synthesized by osteocytes in the regularly distributed osteocytic lacunar canalicular system established after physiological bone remodeling. J Electron Microsc (Tokyo) 58:381–392CrossRef
2.
go back to reference 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 FGF23. Bone 40:1565–1573PubMedCrossRef 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 FGF23. Bone 40:1565–1573PubMedCrossRef
3.
go back to reference Krajisnik T, Bjorklund P, Marsell R, Ljunggren O, Akerstrom G, Jonsson KB, Westin G, Larsson TE (2007) Fibroblast growth factor-23 regulates parathyroid hormone and 1alpha-hydroxylase expression in cultured bovine parathyroid cells. J Endocrinol 195:125–131PubMedCrossRef Krajisnik T, Bjorklund P, Marsell R, Ljunggren O, Akerstrom G, Jonsson KB, Westin G, Larsson TE (2007) Fibroblast growth factor-23 regulates parathyroid hormone and 1alpha-hydroxylase expression in cultured bovine parathyroid cells. J Endocrinol 195:125–131PubMedCrossRef
4.
go back to reference Ben-Dov IZ, Galitzer H, Lavi-Moshayoff V, Goetz R, Kuro-o M, Mohammadi M, Sirkis R, Naveh-Many T, Silver J (2007) The parathyroid is a target organ for FGF23 in rats. J Clin Invest 117:4003–4008PubMed Ben-Dov IZ, Galitzer H, Lavi-Moshayoff V, Goetz R, Kuro-o M, Mohammadi M, Sirkis R, Naveh-Many T, Silver J (2007) The parathyroid is a target organ for FGF23 in rats. J Clin Invest 117:4003–4008PubMed
5.
go back to reference 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 444:770–774PubMedCrossRef 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 444:770–774PubMedCrossRef
6.
go back to reference Kuro-o M (2006) Klotho as a regulator of fibroblast growth factor signaling and phosphate/calcium metabolism. Curr Opin Nephrol Hypertens 15:437–441PubMedCrossRef Kuro-o M (2006) Klotho as a regulator of fibroblast growth factor signaling and phosphate/calcium metabolism. Curr Opin Nephrol Hypertens 15:437–441PubMedCrossRef
7.
8.
go back to reference Shimada T, Kakitani M, Yamazaki Y, Hasegawa H, Takeuchi Y, Fujita T, Fukumoto S, Tomizuka K, Yamashita T (2004) Targeted ablation of FGF23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism. J Clin Invest 113:561–568PubMed Shimada T, Kakitani M, Yamazaki Y, Hasegawa H, Takeuchi Y, Fujita T, Fukumoto S, Tomizuka K, Yamashita T (2004) Targeted ablation of FGF23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism. J Clin Invest 113:561–568PubMed
9.
go back to reference Yoshida T, Fujimori T, Nabeshima Y (2002) Mediation of unusually high concentrations of 1,25-dihydroxyvitamin D in homozygous Klotho mutant mice by increased expression of renal 1alpha-hydroxylase gene. Endocrinology 143:683–689PubMedCrossRef Yoshida T, Fujimori T, Nabeshima Y (2002) Mediation of unusually high concentrations of 1,25-dihydroxyvitamin D in homozygous Klotho mutant mice by increased expression of renal 1alpha-hydroxylase gene. Endocrinology 143:683–689PubMedCrossRef
10.
go back to reference 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 281:6120–6123PubMedCrossRef 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 281:6120–6123PubMedCrossRef
11.
go back to reference ADHR Consortium (2000) Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23. Nat Genet 26:345–348CrossRef ADHR Consortium (2000) Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23. Nat Genet 26:345–348CrossRef
12.
go back to reference Jonsson KB, Zahradnik R, Larsson T, White KE, Sugimoto T, Imanishi Y, Yamamoto T, Hampson G, Koshiyama H, Ljunggren O, Oba K, Yang IM, Miyauchi A, Econs MJ, Lavigne J, Juppner H (2003) Fibroblast growth factor 23 in oncogenic osteomalacia and X-linked hypophosphatemia. N Engl J Med 348:1656–1663PubMedCrossRef Jonsson KB, Zahradnik R, Larsson T, White KE, Sugimoto T, Imanishi Y, Yamamoto T, Hampson G, Koshiyama H, Ljunggren O, Oba K, Yang IM, Miyauchi A, Econs MJ, Lavigne J, Juppner H (2003) Fibroblast growth factor 23 in oncogenic osteomalacia and X-linked hypophosphatemia. N Engl J Med 348:1656–1663PubMedCrossRef
13.
go back to reference Sitara D, Kim S, Razzaque MS, Bergwitz C, Taguchi T, Schuler C, Erben RG, Lanske B (2008) Genetic evidence of serum phosphate-independent functions of FGF-23 on bone. PLoS Genet 4:e1000154PubMedCrossRef Sitara D, Kim S, Razzaque MS, Bergwitz C, Taguchi T, Schuler C, Erben RG, Lanske B (2008) Genetic evidence of serum phosphate-independent functions of FGF-23 on bone. PLoS Genet 4:e1000154PubMedCrossRef
14.
go back to reference 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 49:636–643PubMedCrossRef 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 49:636–643PubMedCrossRef
15.
go back to reference Raimann A, Ertl DA, Helmreich M, Sagmeister S, Egerbacher M, Haeusler G (2013) Fibroblast growth factor 23 and Klotho are present in the growth plate. Connect Tissue Res 54:108–117PubMedCrossRef Raimann A, Ertl DA, Helmreich M, Sagmeister S, Egerbacher M, Haeusler G (2013) Fibroblast growth factor 23 and Klotho are present in the growth plate. Connect Tissue Res 54:108–117PubMedCrossRef
16.
go back to reference Meunier P, Aaron J, Edouard C, Vignon G (1971) Osteoporosis and the replacement of cell populations of the marrow by adipose tissue. A quantitative study of 84 iliac bone biopsies. Clin Orthop Relat Res 80:147–154PubMedCrossRef Meunier P, Aaron J, Edouard C, Vignon G (1971) Osteoporosis and the replacement of cell populations of the marrow by adipose tissue. A quantitative study of 84 iliac bone biopsies. Clin Orthop Relat Res 80:147–154PubMedCrossRef
17.
go back to reference Justesen J, Stenderup K, Ebbesen EN, Mosekilde L, Steiniche T, Kassem M (2001) Adipocyte tissue volume in bone marrow is increased with aging and in patients with osteoporosis. Biogerontology 2:165–171PubMedCrossRef Justesen J, Stenderup K, Ebbesen EN, Mosekilde L, Steiniche T, Kassem M (2001) Adipocyte tissue volume in bone marrow is increased with aging and in patients with osteoporosis. Biogerontology 2:165–171PubMedCrossRef
18.
go back to reference Li Y, He X, He J, Anderstam B, Andersson G, Lindgren U (2011) Nicotinamide phosphoribosyltransferase (Nampt) affects the lineage fate determination of mesenchymal stem cells: a possible cause for reduced osteogenesis and increased adipogenesis in older individuals. J Bone Miner Res 26:2656–2664PubMedCrossRef Li Y, He X, He J, Anderstam B, Andersson G, Lindgren U (2011) Nicotinamide phosphoribosyltransferase (Nampt) affects the lineage fate determination of mesenchymal stem cells: a possible cause for reduced osteogenesis and increased adipogenesis in older individuals. J Bone Miner Res 26:2656–2664PubMedCrossRef
19.
go back to reference Kawaguchi H, Manabe N, Chikuda H, Nakamura K, Kuroo M (2000) Cellular and molecular mechanism of low-turnover osteopenia in the Klotho-deficient mouse. Cell Mol Life Sci 57:731–737PubMedCrossRef Kawaguchi H, Manabe N, Chikuda H, Nakamura K, Kuroo M (2000) Cellular and molecular mechanism of low-turnover osteopenia in the Klotho-deficient mouse. Cell Mol Life Sci 57:731–737PubMedCrossRef
20.
go back to reference DeLuca S, Sitara D, Kang K, Marsell R, Jonsson K, Taguchi T, Erben RG, Razzaque MS, Lanske B (2008) Amelioration of the premature ageing-like features of FGF-23 knockout mice by genetically restoring the systemic actions of FGF-23. J Pathol 216:345–355PubMedCrossRef DeLuca S, Sitara D, Kang K, Marsell R, Jonsson K, Taguchi T, Erben RG, Razzaque MS, Lanske B (2008) Amelioration of the premature ageing-like features of FGF-23 knockout mice by genetically restoring the systemic actions of FGF-23. J Pathol 216:345–355PubMedCrossRef
21.
go back to reference Olauson H, Lindberg K, Amin R, Jia T, Wernerson A, Andersson G, Larsson TE (2012) Targeted deletion of Klotho in kidney distal tubule disrupts mineral metabolism. J Am Soc Nephrol 23:1641–1651PubMedCrossRef Olauson H, Lindberg K, Amin R, Jia T, Wernerson A, Andersson G, Larsson TE (2012) Targeted deletion of Klotho in kidney distal tubule disrupts mineral metabolism. J Am Soc Nephrol 23:1641–1651PubMedCrossRef
22.
go back to reference Daniel WW (1995) Biostatistics: a foundation for analysis in the health sciences. Wiley, New York Daniel WW (1995) Biostatistics: a foundation for analysis in the health sciences. Wiley, New York
23.
go back to reference Montgomery DC (1991) Design and analysis of experiments. Wiley, New York Montgomery DC (1991) Design and analysis of experiments. Wiley, New York
24.
go back to reference Kuro-o M, Matsumura Y, Aizawa H, Kawaguchi H, Suga T, Utsugi T, Ohyama Y, Kurabayashi M, Kaname T, Kume E, Iwasaki H, Iida A, Shiraki-Iida T, Nishikawa S, Nagai R, Nabeshima YI (1997) Mutation of the mouse Klotho gene leads to a syndrome resembling ageing. Nature 390:45–51PubMedCrossRef Kuro-o M, Matsumura Y, Aizawa H, Kawaguchi H, Suga T, Utsugi T, Ohyama Y, Kurabayashi M, Kaname T, Kume E, Iwasaki H, Iida A, Shiraki-Iida T, Nishikawa S, Nagai R, Nabeshima YI (1997) Mutation of the mouse Klotho gene leads to a syndrome resembling ageing. Nature 390:45–51PubMedCrossRef
25.
go back to reference Hume DA, Allan W, Golder J, Stephens RW, Doe WF, Warren HS (1985) Preparation and characterization of human bone marrow-derived macrophages. J Leukoc Biol 38:541–552PubMed Hume DA, Allan W, Golder J, Stephens RW, Doe WF, Warren HS (1985) Preparation and characterization of human bone marrow-derived macrophages. J Leukoc Biol 38:541–552PubMed
26.
go back to reference Ortega E, Garcia JJ, De la Fuente M (2000) Modulation of adherence and chemotaxis of macrophages by norepinephrine. Influence of ageing. Mol Cell Biochem 203:113–117PubMedCrossRef Ortega E, Garcia JJ, De la Fuente M (2000) Modulation of adherence and chemotaxis of macrophages by norepinephrine. Influence of ageing. Mol Cell Biochem 203:113–117PubMedCrossRef
27.
go back to reference Phinney DG, Kopen G, Isaacson RL, Prockop DJ (1999) Plastic adherent stromal cells from the bone marrow of commonly used strains of inbred mice: variations in yield, growth, and differentiation. J Cell Biochem 72:570–585PubMedCrossRef Phinney DG, Kopen G, Isaacson RL, Prockop DJ (1999) Plastic adherent stromal cells from the bone marrow of commonly used strains of inbred mice: variations in yield, growth, and differentiation. J Cell Biochem 72:570–585PubMedCrossRef
28.
go back to reference Li SA, Watanabe M, Yamada H, Nagai A, Kinuta M, Takei K (2004) Immunohistochemical localization of Klotho protein in brain, kidney, and reproductive organs of mice. Cell Struct Funct 29:91–99PubMedCrossRef Li SA, Watanabe M, Yamada H, Nagai A, Kinuta M, Takei K (2004) Immunohistochemical localization of Klotho protein in brain, kidney, and reproductive organs of mice. Cell Struct Funct 29:91–99PubMedCrossRef
29.
go back to reference Fon Tacer K, Bookout AL, Ding X, Kurosu H, John GB, Wang L, Goetz R, Mohammadi M, Kuro-o M, Mangelsdorf DJ, Kliewer SA (2010) Research resource: comprehensive expression atlas of the fibroblast growth factor system in adult mouse. Mol Endocrinol 24:2050–2064PubMedCrossRef Fon Tacer K, Bookout AL, Ding X, Kurosu H, John GB, Wang L, Goetz R, Mohammadi M, Kuro-o M, Mangelsdorf DJ, Kliewer SA (2010) Research resource: comprehensive expression atlas of the fibroblast growth factor system in adult mouse. Mol Endocrinol 24:2050–2064PubMedCrossRef
30.
go back to reference Mohammadi M, McMahon G, Sun L, Tang C, Hirth P, Yeh BK, Hubbard SR, Schlessinger J (1997) Structures of the tyrosine kinase domain of fibroblast growth factor receptor in complex with inhibitors. Science 276:955–960PubMedCrossRef Mohammadi M, McMahon G, Sun L, Tang C, Hirth P, Yeh BK, Hubbard SR, Schlessinger J (1997) Structures of the tyrosine kinase domain of fibroblast growth factor receptor in complex with inhibitors. Science 276:955–960PubMedCrossRef
31.
go back to reference Fliser D, Kollerits B, Neyer U, Ankerst DP, Lhotta K, Lingenhel A, Ritz E, Kronenberg F, Kuen E, Konig P, Kraatz G, Mann JF, Muller GA, Kohler H, Riegler P (2007) Fibroblast growth factor 23 (FGF23) predicts progression of chronic kidney disease: the mild to moderate kidney disease (MMKD) study. J Am Soc Nephrol 18:2600–2608PubMedCrossRef Fliser D, Kollerits B, Neyer U, Ankerst DP, Lhotta K, Lingenhel A, Ritz E, Kronenberg F, Kuen E, Konig P, Kraatz G, Mann JF, Muller GA, Kohler H, Riegler P (2007) Fibroblast growth factor 23 (FGF23) predicts progression of chronic kidney disease: the mild to moderate kidney disease (MMKD) study. J Am Soc Nephrol 18:2600–2608PubMedCrossRef
32.
go back to reference Gutierrez OM, Mannstadt M, Isakova T, Rauh-Hain JA, Tamez H, Shah A, Smith K, Lee H, Thadhani R, Juppner H, Wolf M (2008) Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med 359:584–592PubMedCrossRef Gutierrez OM, Mannstadt M, Isakova T, Rauh-Hain JA, Tamez H, Shah A, Smith K, Lee H, Thadhani R, Juppner H, Wolf M (2008) Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med 359:584–592PubMedCrossRef
33.
go back to reference Gutierrez OM, Januzzi JL, Isakova T, Laliberte K, Smith K, Collerone G, Sarwar A, Hoffmann U, Coglianese E, Christenson R, Wang TJ, deFilippi C, Wolf M (2009) Fibroblast growth factor 23 and left ventricular hypertrophy in chronic kidney disease. Circulation 119:2545–2552PubMedCrossRef Gutierrez OM, Januzzi JL, Isakova T, Laliberte K, Smith K, Collerone G, Sarwar A, Hoffmann U, Coglianese E, Christenson R, Wang TJ, deFilippi C, Wolf M (2009) Fibroblast growth factor 23 and left ventricular hypertrophy in chronic kidney disease. Circulation 119:2545–2552PubMedCrossRef
34.
go back to reference Seiler S, Reichart B, Roth D, Seibert E, Fliser D, Heine GH (2010) FGF-23 and future cardiovascular events in patients with chronic kidney disease before initiation of dialysis treatment. Nephrol Dial Transpl 25:3983–3989CrossRef Seiler S, Reichart B, Roth D, Seibert E, Fliser D, Heine GH (2010) FGF-23 and future cardiovascular events in patients with chronic kidney disease before initiation of dialysis treatment. Nephrol Dial Transpl 25:3983–3989CrossRef
35.
go back to reference Mirza MA, Karlsson MK, Mellstrom D, Orwoll E, Ohlsson C, Ljunggren O, Larsson TE (2011) Serum fibroblast growth factor-23 (FGF23) and fracture risk in elderly men. J Bone Miner Res 26:857–864PubMedCrossRef Mirza MA, Karlsson MK, Mellstrom D, Orwoll E, Ohlsson C, Ljunggren O, Larsson TE (2011) Serum fibroblast growth factor-23 (FGF23) and fracture risk in elderly men. J Bone Miner Res 26:857–864PubMedCrossRef
36.
go back to reference Mirza MA, Alsio J, Hammarstedt A, Erben RG, Michaelsson K, Tivesten A, Marsell R, Orwoll E, Karlsson MK, Ljunggren O, Mellstrom D, Lind L, Ohlsson C, Larsson TE (2011) Circulating fibroblast growth factor-23 is associated with fat mass and dyslipidemia in two independent cohorts of elderly individuals. Arter Thromb Vasc Biol 31:219–227CrossRef Mirza MA, Alsio J, Hammarstedt A, Erben RG, Michaelsson K, Tivesten A, Marsell R, Orwoll E, Karlsson MK, Ljunggren O, Mellstrom D, Lind L, Ohlsson C, Larsson TE (2011) Circulating fibroblast growth factor-23 is associated with fat mass and dyslipidemia in two independent cohorts of elderly individuals. Arter Thromb Vasc Biol 31:219–227CrossRef
37.
go back to reference Mirza MA, Hansen T, Johansson L, Ahlstrom H, Larsson A, Lind L, Larsson TE (2009) Relationship between circulating FGF23 and total body atherosclerosis in the community. Nephrol Dial Transpl 24:3125–3131CrossRef Mirza MA, Hansen T, Johansson L, Ahlstrom H, Larsson A, Lind L, Larsson TE (2009) Relationship between circulating FGF23 and total body atherosclerosis in the community. Nephrol Dial Transpl 24:3125–3131CrossRef
38.
go back to reference Mirza MA, Larsson A, Lind L, Larsson TE (2009) Circulating fibroblast growth factor-23 is associated with vascular dysfunction in the community. Atherosclerosis 205:385–390PubMedCrossRef Mirza MA, Larsson A, Lind L, Larsson TE (2009) Circulating fibroblast growth factor-23 is associated with vascular dysfunction in the community. Atherosclerosis 205:385–390PubMedCrossRef
39.
go back to reference Chung UI, Kawaguchi H, Takato T, Nakamura K (2004) Distinct osteogenic mechanisms of bones of distinct origins. J Orthop Sci 9:410–414PubMedCrossRef Chung UI, Kawaguchi H, Takato T, Nakamura K (2004) Distinct osteogenic mechanisms of bones of distinct origins. J Orthop Sci 9:410–414PubMedCrossRef
40.
go back to reference 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 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
41.
go back to reference Shalhoub V, Ward SC, Sun B, Stevens J, Renshaw L, Hawkins N, Richards WG (2011) Fibroblast growth factor 23 (FGF23) and alpha-Klotho stimulate osteoblastic MC3T3.E1 cell proliferation and inhibit mineralization. Calcif Tissue Int 89:140–150PubMedCrossRef Shalhoub V, Ward SC, Sun B, Stevens J, Renshaw L, Hawkins N, Richards WG (2011) Fibroblast growth factor 23 (FGF23) and alpha-Klotho stimulate osteoblastic MC3T3.E1 cell proliferation and inhibit mineralization. Calcif Tissue Int 89:140–150PubMedCrossRef
42.
go back to reference Kawai M, Kinoshita S, Kimoto A, Hasegawa Y, Miyagawa K, Yamazaki M, Ohata Y, Ozono K, Michigami T (2013) FGF23 suppresses chondrocyte proliferation in the presence of soluble alpha-Klotho both in vitro and in vivo. J Biol Chem 288:2414–2427PubMedCrossRef Kawai M, Kinoshita S, Kimoto A, Hasegawa Y, Miyagawa K, Yamazaki M, Ohata Y, Ozono K, Michigami T (2013) FGF23 suppresses chondrocyte proliferation in the presence of soluble alpha-Klotho both in vitro and in vivo. J Biol Chem 288:2414–2427PubMedCrossRef
43.
go back to reference Marsell R, Mirza MA, Mallmin H, Karlsson M, Mellstrom D, Orwoll E, Ohlsson C, Jonsson KB, Ljunggren O, Larsson TE (2009) Relation between fibroblast growth factor-23, body weight and bone mineral density in elderly men. Osteoporos Int 20:1167–1173PubMedCrossRef Marsell R, Mirza MA, Mallmin H, Karlsson M, Mellstrom D, Orwoll E, Ohlsson C, Jonsson KB, Ljunggren O, Larsson TE (2009) Relation between fibroblast growth factor-23, body weight and bone mineral density in elderly men. Osteoporos Int 20:1167–1173PubMedCrossRef
44.
go back to reference Chai Y, Jiang X, Ito Y, Bringas P Jr, Han J, Rowitch DH, Soriano P, McMahon AP, Sucov HM (2000) Fate of the mammalian cranial neural crest during tooth and mandibular morphogenesis. Development 127:1671–1679PubMed Chai Y, Jiang X, Ito Y, Bringas P Jr, Han J, Rowitch DH, Soriano P, McMahon AP, Sucov HM (2000) Fate of the mammalian cranial neural crest during tooth and mandibular morphogenesis. Development 127:1671–1679PubMed
46.
go back to reference Oklund SA, Prolo DJ, Gutierrez RV, King SE (1986) Quantitative comparisons of healing in cranial fresh autografts, frozen autografts and processed autografts, and allografts in canine skull defects. Clin Orthop Relat Res 205:269–291PubMed Oklund SA, Prolo DJ, Gutierrez RV, King SE (1986) Quantitative comparisons of healing in cranial fresh autografts, frozen autografts and processed autografts, and allografts in canine skull defects. Clin Orthop Relat Res 205:269–291PubMed
47.
go back to reference Akintoye SO, Lam T, Shi S, Brahim J, Collins MT, Robey PG (2006) Skeletal site-specific characterization of orofacial and iliac crest human bone marrow stromal cells in same individuals. Bone 38:758–768PubMedCrossRef Akintoye SO, Lam T, Shi S, Brahim J, Collins MT, Robey PG (2006) Skeletal site-specific characterization of orofacial and iliac crest human bone marrow stromal cells in same individuals. Bone 38:758–768PubMedCrossRef
48.
go back to reference van den Bos T, Speijer D, Bank RA, Bromme D, Everts V (2008) Differences in matrix composition between calvaria and long bone in mice suggest differences in biomechanical properties and resorption: special emphasis on collagen. Bone 43:459–468PubMedCrossRef van den Bos T, Speijer D, Bank RA, Bromme D, Everts V (2008) Differences in matrix composition between calvaria and long bone in mice suggest differences in biomechanical properties and resorption: special emphasis on collagen. Bone 43:459–468PubMedCrossRef
49.
go back to reference Blair HC, Zaidi M, Schlesinger PH (2002) Mechanisms balancing skeletal matrix synthesis and degradation. Biochem J 364:329–341PubMedCrossRef Blair HC, Zaidi M, Schlesinger PH (2002) Mechanisms balancing skeletal matrix synthesis and degradation. Biochem J 364:329–341PubMedCrossRef
51.
go back to reference 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 280:19883–19887PubMedCrossRef 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 280:19883–19887PubMedCrossRef
52.
go back to reference Winkler DG, Sutherland MS, Ojala E, Turcott E, Geoghegan JC, Shpektor D, Skonier JE, Yu C, Latham JA (2005) Sclerostin inhibition of Wnt-3a-induced C3H10T1/2 cell differentiation is indirect and mediated by bone morphogenetic proteins. J Biol Chem 280:2498–2502PubMedCrossRef Winkler DG, Sutherland MS, Ojala E, Turcott E, Geoghegan JC, Shpektor D, Skonier JE, Yu C, Latham JA (2005) Sclerostin inhibition of Wnt-3a-induced C3H10T1/2 cell differentiation is indirect and mediated by bone morphogenetic proteins. J Biol Chem 280:2498–2502PubMedCrossRef
Metadata
Title
FGF23 Affects the Lineage Fate Determination of Mesenchymal Stem Cells
Authors
Yan Li
Xu He
Hannes Olauson
Tobias E. Larsson
Urban Lindgren
Publication date
01-12-2013
Publisher
Springer US
Published in
Calcified Tissue International / Issue 6/2013
Print ISSN: 0171-967X
Electronic ISSN: 1432-0827
DOI
https://doi.org/10.1007/s00223-013-9795-6

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