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Effect of Fibroblast Growth Factor 23 on Osteoblastic Differentiation and Mineralization of D1 Mesenchymal Stem Cells
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  • Journal title : Journal of Life Science
  • Volume 26, Issue 3,  2016, pp.331-337
  • Publisher : Korean Society of Life Science
  • DOI : 10.5352/JLS.2016.26.3.331
 Title & Authors
Effect of Fibroblast Growth Factor 23 on Osteoblastic Differentiation and Mineralization of D1 Mesenchymal Stem Cells
Park, Kyeong-Lok;
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 Abstract
Although fibroblast growth factor 23 (FGF23) is exclusively produced in osteoblasts and osteocytes, its main target is the kidney, where it decreases phosphate reabsorption by suppressing Na-phosphate cotransporters. Independently of its action on phosphate homeostasis, FGF23 also inhibits bone formation in vivo. In a calvarial osteoblastic cell model, FGF23 was shown to negatively affect extracellular matrix mineralization. This study investigated whether FGF23 had similar effects on osteoblast maturation, including differentiation and mineralization of bone marrow-derived mesenchymal stem cells (MSCs). D1 MSCs were cultured in an osteogenic medium containing β-glycerophosphate, ascorbic acid, and dexamethazone. Osteoblastic differentiation was evaluated by alkaline phosphatase (Alp) staining, and matrix mineralization was evaluated by alizarin red staining and calcium deposition. The expression of differentiation-stimulating genes Runx2, Alp, and osteocalcin and mineralization-inhibiting genes Enpp1 and Ank was analyzed using semiquantitative RT-PCR. Supraphysiological doses of FGF23 did not stimulate proliferation or osteoblastic differentiation of MSCs. Matrix mineralization 1, 2, and 3 weeks after the FGF23 treatment did not vary between control and FGF23 groups, although time-dependent enhancement of mineralization was obvious. Calcium deposition was also unchanged after the FGF23 treatment. mRNA expression levels of differentiation- and mineralization-related genes were also similar between the groups. Despite these negative findings, FGF23 signaling through FGF receptors seemed to function normally, with phosphorylation of the Erk protein more evident in the FGF23 group than in controls. These findings suggest that unlike calvarial osteoblasts, FGF23 is not likely to affect osteoblastic differentiation and mineralization of MSCs.
 Keywords
Differentiation;fibroblast growth factor 23;mesenchymal stem cell;mineralization;
 Language
Korean
 Cited by
 References
1.
Akintoye, S. O., Lam, T., Shi, S., Brahim, J., Collins, M. T. and Robey, P. G. 2006. Skeletal site-specific characterization of orofacial and iliac crest human bone marrow stromal cells in same individuals. Bone 38, 758-768. crossref(new window)

2.
Aubin, J. E. 2001. Regulation of osteoblast formation and function. Rev. Endocr. Metab. Disord. 2, 81-94. crossref(new window)

3.
Fukumoto, S. 2009. The role of bone in phosphate metabolism. Mol. Cell Endocrinol. 310, 63-70. crossref(new window)

4.
Helms, J. A. and Schneider, R. A. 2003. Cranial skeletal biology. Nature 423, 326-331. crossref(new window)

5.
Hessle, L., Johnson, K. A., Anderson, H. C., Narisawa, S., Sali, A., Goding, J. W., Terkeltaub, R. and Millan, J. L. 2002. Tissue-nonspecific alkaline phosphatase and plasma cell membrane glycoprotein-1 are central antagonistic regulators of bone mineralization. Proc. Natl. Acad. Sci. USA 99, 9445-9449. crossref(new window)

6.
Hui, M. and Tenenbaum, H. C. 1998. New face of an old enzyme: alkaline phosphatase may contribute to human tissue aging by inducing tissue hardening and calcification. Anat. Rec. 253, 91-94. crossref(new window)

7.
Jonsson, K. B., Zahradnik, R., Larsson, T., White, K. E., Sugimoto, T., Imanishi, Y., Yamamoto, T., Hampson, G., Koshiyama, H., Ljunggren, O., Oba, K., Yang, I. M., Miyauchi, A., Econs, M. J., Lavigne, J. and Juppner, H. 2003. Fibroblast growth factor 23 in oncogenic osteomalacia and X-linked hypophosphatemia. N. Engl. J. Med. 348, 1656-1663. crossref(new window)

8.
Juffroy, O., Noel, D., Delanoye, A., Viltart, O., Wolowczuk, I. and Verwaerde, C. 2009. Subcutaneous graft of D1 mouse mesenchymal stem cells leads to the formation of a bone-like structure. Differentiation 78, 223-231. crossref(new window)

9.
Larsson, T., Marsell, R., Schipani, E., Ohlsson, C., Ljunggren, O., Tenenhouse, H. S., Juppner, H. and Jonsson, K. B. 2004. 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 145, 3087-3094. crossref(new window)

10.
Li, Y., He, X., Olauson, H., Larsson, T. E. and Lindgren, U. 2013. FGF23 affects the lineage fate determination of mesenchymal stem cells. Calcif. Tissue Int. 93, 556-564. crossref(new window)

11.
Murali, S. K., Roschger, P., Zeitz, U., Klaushofer, K., Andrukhova, O. and Erben, R. G. 2016. FGF23 regulates bone mineralization in a 1,25(OH) D and Klotho-Independent manner. J. Bone Miner. Res. 31, 129-142. crossref(new window)

12.
Perwad, F., Zhang, M. Y., Tenenhouse, H. S. and Portale, A. A. 2007. Fibroblast growth factor 23 impairs phosphorus and vitamin D metabolism in vivo and suppresses 25- hydroxyvitamin D-1Alpha-hydroxylase expression in vitro. Am. J. Physiol. Renal Physiol. 293, F1577-1583. crossref(new window)

13.
Quarles, L. D. 2012. Skeletal secretion of FGF-23 regulates phosphate and vitamin D metabolism. Nat. Rev. Endocrinol. 8, 276-286. crossref(new window)

14.
Quarto, N., Wan, D. C., Kwan, M. D., Panetta, N. J., Li, S. and Longaker, M. T. 2010. Origin matters: differences in embryonic tissue origin and Wnt signaling determine the osteogenic potential and healing capacity of frontal and parietal calvarial bones. J. Bone Miner. Res. 25, 1680-1694.

15.
Razzaque, M. S. and Lanske, B. 2007. The emerging role of the fibroblast growth factor-23-Klotho axis in renal regulation of phosphate homeostasis. J. Endocrinol. 194, 1-10. crossref(new window)

16.
Saji, F., Shigematsu, T., Sakaguchi, T., Ohya, M., Orita, H., Maeda, Y., Ooura, M., Mima, T. and Negi, S. 2010. Fibroblast growth factor 23 production in bone is directly regulated by 1{Alpha},25-dihydroxyvitamin D, but not PTH. Am. J. Physiol. Renal Physiol. 299, F1212-1217. crossref(new window)

17.
Shalhoub, V., Ward, S. C., Sun, B., Stevens, J., Renshaw, L., Hawkins, N. and Richards, W. G. 2011. Fibroblast growth factor 23 (FGF23) and Alpha-Klotho stimulate osteoblastic MC3T3.E1 cell proliferation and inhibit mineralization. Calcif. Tissue Int. 89, 140-150. crossref(new window)

18.
Shimada, T., Kakitani, M., Yamazaki, Y., Hasegawa, H., Takeuchi, Y., Fujita, T., Fukumoto, S., Tomizuka, K. and Yamashita, T. 2004. Targeted ablation of Fgf23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism. J. Clin. Invest. 113, 561-568. crossref(new window)

19.
Sitara, D. 2007. Correlation among hyperphosphatemia, type II sodium phosphate transporter activity, and vitamin D metabolism in Fgf-23 null mice. Ann. N Y Acad. Sci. 1116, 485-493. crossref(new window)

20.
Sitara, D., Kim, S., Razzaque, M. S., Bergwitz, C., Taguchi, T., Schuler, C., Erben, R. G. and Lanske, B. 2008. Genetic evidence of serum phosphate-independent functions of FGF-23 on bone. PLoS Genet. 4, e1000154. crossref(new window)

21.
Takei, Y., Minamizaki, T. and Yoshiko, Y. 2015. Functional diversity of fibroblast growth factors in bone formation. Int. J. Endocrinol. 2015, 729352.

22.
Urakawa, I., Yamazaki, Y., Shimada, T., Iijima, K., Hasegawa, H., Okawa, K., Fujita, T., Fukumoto, S. and Yamashita, T. 2006. Klotho converts canonical FGF receptor into a specific receptor for FGF23. Nature 444, 770-774. crossref(new window)

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

24.
Xiao, L., Esliger, A. and Hurley, M. M. 2013. Nuclear fibroblast growth factor 2 (FGF2) isoforms inhibit bone marrow stromal cell mineralization through FGF23/FGFR/MAPK in vitro. J. Bone Miner. Res. 28, 35-45. crossref(new window)

25.
Xiao, L., Naganawa, T., Lorenzo, J., Carpenter, T. O., Coffin, J. D. and Hurley, M. M. 2010. Nuclear isoforms of fibroblast growth factor 2 are novel inducers of hypophosphatemia via modulation of FGF23 and KLOTHO. J. Biol. Chem. 285, 2834-2846. crossref(new window)

26.
Zadik, Y. and Nitzan, D. W. 2012. Tumor induced osteomalacia: a forgotten paraneoplastic syndrome? Oral Oncol. 48, e9-10. crossref(new window)