Abstract
Fibroblast growth factors (FGFs) regulate the proliferation and differentiation of various cells via their respective receptors (FGFRs). During the early stages of tooth development in fetal mice, FGFs and FGFRs have been shown to be expressed in dental epithelia and mesenchymal cells at the initial stages of odontogenesis and to regulate cell proliferation and differentiation. However, little is known about the expression patterns of FGFs in the advanced stages of tooth development. In the present study, we focused on FGF18 expression in the rat mandibular first molar (M1) during the postnatal crown and root formation stages. FGF18 signals by RT-PCR using cDNAs from M1 were very weak at postnatal day 5 and were significantly up-regulated at days 7, 9 and 15. Transcripts were undetectable by in situ hybridization (ISH) but could be detected by in situ RT-PCR in the differentiated odontoblasts and cells of the sub-odontoblastic layer in both crown and root portions of M1 at day 15. The transcripts of FGFR2c and FGFR3, possible candidate receptors of FGF18, were detected by RT-PCR and ISH in differentiated odontoblasts throughout postnatal development. These results suggest the continual involvement of FGF18 signaling in the regulation of odontoblasts during root formation where it may contribute to dentin matrix formation and/or mineralization.
Similar content being viewed by others
References
Armelin HA. Pituitary extracts and steroid hormones in the control of 3T3 cell growth. Proc Nat Acad Sci USA. 1973;70:2702–6.
Powers CJ, McLeskey SW, Wellstein A. Fibroblast growth factors, their receptors and signaling. Endocr Relat Cancer. 2000;7:165–97.
Bugler B, Amalric F, Prats H. Alternative initiation of translation determines cytoplasmic or nuclear localization of basic fibroblast growth factor. Mol Cell Biol. 1991;11:573–7.
Quarto N, Finger FP, Rifkin DB. The NH2-terminal extension of high molecular weight bFGF is a nuclear targeting signal. J Cell Physiol. 1991;147:311–8.
Imamura T, Tokita Y, Mitsui Y. Identification of a heparin-binding growth factor-1 nuclear translocation sequence by deletion mutation analysis. J Biol Chem. 1992;267:5676–9.
Kettunen P, Thesleff I. Expression and function of FGFs-4, -8, and -9 suggest functional redundancy and repetitive use as epithelial signals during tooth morphogenesis. Dev Dyn. 1998;211:256–68.
Jernvall J, Kettunen P, Karavanova I, Martin LB, Thesleff I. Evidence for the role the enamel knot as a control center in mammalian tooth cusp formation: non-dividing cells express growth stimulating Fgf-4 gene. Int J Dev Biol. 1994;38:463–9.
Orr-Urtreger A, Givol D, Yayon A, Yarden Y, Lonai P. Developmental expression of two murine fibroblast growth factor receptors, flg and bek. Development. 1991;113:1419–34.
Peters KG, Werner S, Chen G, Williams LT. Two FGF receptor genes are differentially expressed in epithelial and mesenchymal tissues during limb formation and organogenesis in the mouse. Development. 1992;114:223–43.
Kettunen P, Karavanova I, Thesleff I. Responsiveness of developing dental tissues to fibroblast growth factors: expression of splicing alternatives of FGFR1, -2, -3, and of FGFR4; and stimulation of cell proliferation by FGF-2, -4, -8, and -9. Dev Genet. 1998;22:374–85.
Reinhold MI, Naski MC. Direct interactions of Runx2 and canonical Wnt signaling induce FGF18. J Biol Chem. 2007;282:3653–63.
Chen J, Lan Y, Baek J-A, Gao Y, Jiang R. Wnt/beta-catenin signaling plays an essential role in activation of odontogenic mesenchyme during early tooth development. Dev Biol. 2009;334:174–85.
Yamashiro T, Zheng L, Shitaku Y, Saito M, Tsubakimoto T, Takada K, Takano-Yamamoto T, Thesleff I. Wnt10a regulates dentin sialophosphoprotein mRNA expression and possibly links odontoblast differentiation and tooth morphogenesis. Differentiation. 2007;75:452–62.
Kim T-H, Lee J-Y, Baek J-A, Lee J-C, Yang X, Taketo MM, Jiang R, Cho E-S. Consitutive stabilization of β-catenin in the dental mesenchyme leads to excessive dentin and cementum formation. Biochem Biophys Res Commun. 2011;412:549–55.
Peng L, Ren LB, Dong G, Wang CL, Xu P, Ye L, Zhou XD. Wnt5a promotes differentiation of human dental papilla cells. Int Endod J. 2010;43:404–12.
Ohbayashi N, Hoshikawa M, Kimura S, Yamasaki M, Fukui S, Itoh N. Structure and expression of the mRNA encoding a novel fibroblast growth factor, FGF18. J Biol Chem. 1998;29:18161–4.
Itoh N, Ornitz DM. Evolution of the Fgf and Fgfr gene families. Trends Genet. 2004;20:563–9.
Maruoka Y, Ohbayashi N, Hoshikawa M, Itoh N, Hogan BLM, Furuta Y. Comparison of the expression of three highly related genes, Fgf8, Fgf17 and Fgf18, in the mouse embryo. Mech Dev. 1998;74:175–7.
Ohuchi H, Kimura S, Watamoto M, Itoh N. Involvement of fibroblast growth factor (FGF)18-FGF8 signaling in specification of left-right asymmetry and brain and limb development of the chick embryo. Mech Dev. 2000;95:55–66.
Ohbayashi N, Shibayama M, Kurotaki Y, Imanishi M, Fujimori T, Itoh N, Takada S. FGF18 is required for normal cell proliferation and differentiation during osteogenesis and chondrogenesis. Genes Dev. 2002;16:870–9.
Wang H, Yoshiko Y, Yamamoto R, Minamizaki T, Kozai K, Tanne K, Aubin JE, Maeda N. Overexpression of fibroblast growth factor 23 suppresses osteoblast differentiation and matrix mineralization in vitro. J Bone Miner Res. 2008;23:939–48.
Nuovo GJ. PCR in situ Hybridization; Protocols and Applications. 2nd ed. New York: Raven Press; 1994. p. 247–306.
Baba O, Qin C, Brunn JC, Jones JE, Wygant JN, McIntyre BW, Butler WT. Detection of dentin sialoprotein in rat periodontium. Eur J Oral Sci. 2004;112:163–70.
Spann W, Pachmann K, Zabnienska H, Pielmeier A, Emmerich B. In situ amplification of single copy gene segments in individual cells by the polymerase chain reaction. Infection. 1991;19:242–4.
Chen RH, Fuggle SV. In situ cDNA polymerase chain reaction. A novel technique for detecting mRNA expression. Am J Pathol. 1993;143:1527–34.
Acknowledgments
This study was supported by a Grant-in-Aid for Scientific Research (to OB, TT) from the Japan Society for the Promotion of Science (#18591996), and by a Grant for Supporting Project for Strategic Research of Nihon University, School of Dentistry at Matsudo by the Ministry of Education, Culture, Sports, Science and Technology, 2008–2011 (Team: Dental morphogenesis; to OB, TT and MO).
Conflict of interest
All authors declare that they have no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Baba, O., Ota, M.S., Terashima, T. et al. Expression of transcripts for fibroblast growth factor 18 and its possible receptors during postnatal dentin formation in rat molars. Odontology 103, 136–142 (2015). https://doi.org/10.1007/s10266-013-0147-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10266-013-0147-9