Browse > Article
http://dx.doi.org/10.14348/molcells.2017.0019

Effect of FGF-2, TGF-β-1, and BMPs on Teno/Ligamentogenesis and Osteo/Cementogenesis of Human Periodontal Ligament Stem Cells  

Hyun, Sun-Yi (Department of Nanobiomedical Science and BK21 PLUS Global Research Center for Regenerative Medicine, Dankook University)
Lee, Ji-Hye (Department of Nanobiomedical Science and BK21 PLUS Global Research Center for Regenerative Medicine, Dankook University)
Kang, Kyung-Jung (Department of Nanobiomedical Science and BK21 PLUS Global Research Center for Regenerative Medicine, Dankook University)
Jang, Young-Joo (Department of Nanobiomedical Science and BK21 PLUS Global Research Center for Regenerative Medicine, Dankook University)
Abstract
The periodontal ligament (PDL) is the connective tissue between tooth root and alveolar bone containing mesenchymal stem cells (MSC). It has been suggested that human periodontal ligament stem cells (hPDLSCs) differentiate into osteo/cementoblast and ligament progenitor cells. The periodontitis is a representative oral disease where the PDL tissue is collapsed, and regeneration of this tissue is important in periodontitis therapy. Fibroblast growth factor-2 (FGF-2) stimulates proliferation and differentiation of fibroblastic MSCs into various cell lineages. We evaluated the dose efficacy of FGF-2 for cytodifferentiation of hPDLSCs into ligament progenitor. The fibrous morphology was highly stimulated even at low FGF-2 concentrations, and the expression of teno/ligamentogenic markers, scleraxis and tenomodulin in hPDLSCs increased in a dose dependent manner of FGF-2. In contrast, expression of the osteo/cementogenic markers decreased, suggesting that FGF-2 might induce and maintain the ligamentogenic potential of hPDLSCs. Although the stimulation of tenocytic maturation by $TGF-{\beta}1$ was diminished by FGF-2, the inhibition of the expression of early ligamentogenic marker by $TGF-{\beta}1$ was redeemed by FGF-2 treatment. The stimulating effect of BMPs on osteo/cementogenesis was apparently suppressed by FGF-2. These results indicate that FGF-2 predominantly differentiates the hPDLSCs into teno/ligamentogenesis, and has an antagonistic effect on the hard tissue differentiation induced by BMP-2 and BMP-4.
Keywords
bone morphogenic protein (BMP); human fibroblast growth factor 2 (hFGF-2); ligamentogenesis; osteogenesis; periodontal ligament stem cells (PDLSCs); $TGF-{\beta}1$;
Citations & Related Records
연도 인용수 순위
  • Reference
1 de Gorter, D.J., van Dinther, M., Korchynskyi, O., and ten Dijke, P. (2011). Biphasic effects of transforming growth factor beta on bone morphogenetic protein-induced osteoblast differentiation. J. Bone Miner. Res. 26, 1178-1187.   DOI
2 Francis, P.H., Richardson, M.K., Brickell, P.M., and Tickle, C. (1994). Bone morphogenetic proteins and a signalling pathway that controls patterning in the developing chick limb. Development 120, 209-218.
3 Fujii, S., Maeda, H., Tomokiyo, A., Monnouchi, S., Hori, K., Wada, N., and Akamine, A. (2010). Effects of TGF-beta1 on the proliferation and differentiation of human periodontal ligament cells and a human periodontal ligament stem/progenitor cell line. Cell Tissue Res. 342, 233-242.   DOI
4 Itaya, T., Kagami, H., Okada, K., Yamawaki, A., Narita, Y., Inoue, M., Sumita, Y., and Ueda, M. (2009). Characteristic changes of periodontal ligament-derived cells during passage. J. Periodontal. Res. 44, 425-433.   DOI
5 Kao, R.T., Murakami, S., and Beirne, O.R. (2009). The use of biologic mediators and tissue engineering in dentistry. Periodontology 2000 50, 127-153.   DOI
6 Kawahara, T., Yamashita, M., Ikegami, K., Nakamura, T., Yanagita, M., Yamada, S., Kitamura, M., and Murakami, S. (2015). TGF-$\beta$ negatively regulates the BMP2-dependent early commitment of periodontal ligament cells into hard tissue forming cells. PloS one 10, e0125590.   DOI
7 Lai, W.T., Krishnappa, V., and Phinney, D.G. (2011). Fibroblast growth factor 2 (Fgf2) inhibits differentiation of mesenchymal stem cells by inducing Twist2 and Spry4, blocking extracellular regulated kinase activation, and altering Fgf receptor expression levels. Stem Cells 29, 1102-1111.   DOI
8 Lee, T.H., Kim, W.T., Ryu, C.J., and Jang, Y.J. (2015). Optimization of treatment with recombinant FGF-2 for proliferation and differentiation of human dental stem cells, mesenchymal stem cells, and osteoblasts. Biochem. Cell Biol. 93, 298-305.   DOI
9 Lekic, P., and McCulloch, C.A. (1996). Periodontal ligament cell population: the central role of fibroblasts in creating a unique tissue. Anat. Rec. 245, 327-341.   DOI
10 Lorda-Diez, C.I., Montero, J.A., Martinez-Cue, C., Garcia-Porrero, J.A., and Hurle, J.M. (2009). Transforming growth factors beta coordinate cartilage and tendon differentiation in the developing limb mesenchyme. J. Biol. Chem. 284, 29988-29996.   DOI
11 Maeda, H., Tomokiyo, A., Fujii, S., Wada, N., and Akamine, A. (2011). Promise of periodontal ligament stem cells in regeneration of periodontium. Stem Cell Res. Ther. 2, 33.   DOI
12 Terranova, V.P. (1993). Biologically active factors in the treatment of periodontal disease. Curr. Opin. Periodontol. 1993, 129-135.
13 Neubauer, M., Fischbach, C., Bauer-Kreisel, P., Lieb, E., Hacker, M., Tessmar, J., Schulz, M.B., Goepferich, A., and Blunk, T. (2004). Basic fibroblast growth factor enhances PPARgamma ligand-induced adipogenesis of mesenchymal stem cells. FEBS Lett. 577, 277-283.   DOI
14 Olson, E.N., and Capetanaki, Y.G. (1989). Developmental regulation of intermediate filament and actin mRNAs during myogenesis is disrupted by oncogenic ras genes. Oncogene 4, 907-913.
15 Seo, B.M., Miura, M., Gronthos, S., Bartold, P.M., Batouli, S., Brahim, J., Young, M., Robey, P.G., Wang, C.Y., and Shi, S. (2004). Investigation of multipotent postnatal stem cells from human periodontal ligament. Lancet 364, 149-155.   DOI
16 Shi, Y., and Massague, J. (2003). Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell 113, 685-700.   DOI
17 Shimabukuro, Y., Terashima, H., Takedachi, M., Maeda, K., Nakamura, T., Sawada, K., Kobashi, M., Awata, T., Oohara, H., Kawahara, T., et al. (2011). Fibroblast growth factor-2 stimulates directed migration of periodontal ligament cells via PI3K/AKT signaling and CD44/hyaluronan interaction. J. Cell. Physiol. 226, 809-821.   DOI
18 Solchaga, L.A., Penick, K., Porter, J.D., Goldberg, V.M., Caplan, A.I., and Welter, J.F. (2005). FGF-2 enhances the mitotic and chondrogenic potentials of human adult bone marrow-derived mesenchymal stem cells. J. Cell. Physiol. 203, 398-409.   DOI
19 Sugimoto, Y., Takimoto, A., Akiyama, H., Kist, R., Scherer, G., Nakamura, T., Hiraki, Y., and Shukunami, C. (2013). Scx+/Sox9+ progenitors contribute to the establishment of the junction between cartilage and tendon/ligament. Development 140, 2280-2288.   DOI
20 Urist, M.R. (1965). Bone: formation by autoinduction. Science 150, 893-899.   DOI
21 Vainio, S., Karavanova, I., Jowett, A., and Thesleff, I. (1993). Identification of BMP-4 as a signal mediating secondary induction between epithelial and mesenchymal tissues during early tooth development. Cell 75, 45-58.   DOI
22 Wikesjo, U.M., Razi, S.S., Sigurdsson, T.J., Tatakis, D.N., Lee, M.B., Ongpipattanakul, B., Nguyen, T., and Hardwick, R. (1998). Periodontal repair in dogs: effect of recombinant human transforming growth factor-beta1 on guided tissue regeneration. J. Clin. Periodontol. 25, 475-481.   DOI
23 Dangaria, S.J., Ito, Y., Walker, C., Druzinsky, R., Luan, X., and Diekwisch, T.G. (2009). Extracellular matrix-mediated differentiation of periodontal progenitor cells. Differentiation 78, 79-90.   DOI
24 Asano, M., Kubota, S., Nakanishi, T., Nishida, T., Yamaai, T., Yosimichi, G., Ohyama, K., Sugimoto, T., Murayama, Y., and Takigawa, M. (2005). Effect of connective tissue growth factor (CCN2/CTGF) on proliferation and differentiation of mouse periodontal ligament-derived cells. Cell Commun. Signal. 3, 11.   DOI
25 Beertsen, W., McCulloch, C.A., and Sodek, J. (1997). The periodontal ligament: a unique, multifunctional connective tissue. Periodontology 2000 13, 20-40.   DOI
26 Bradfute, S.B., Graubert, T.A., and Goodell, M.A. (2005). Roles of Sca-1 in hematopoietic stem/progenitor cell function. Exp. Hematol. 33, 836-843.   DOI
27 Yanagita, M., Kojima, Y., Kubota, M., Mori, K., Yamashita, M., Yamada, S., Kitamura, M., and Murakami, S. (2014). Cooperative effects of FGF-2 and VEGF-A in periodontal ligament cells. J. Dent. Res. 93, 89-95.   DOI
28 Yu, P.J., Ferrari, G., Galloway, A.C., Mignatti, P., and Pintucci, G. (2007). Basic fibroblast growth factor (FGF-2): the high molecular weight forms come of age. J. Cell. Biochem. 100, 1100-1108.   DOI
29 Choi, J.K., Hwang, H.I., and Jang, Y.J. (2015). The efficiency of the in vitro osteo/dentinogenic differentiation of human dental pulp cells, periodontal ligament cells and gingival fibroblasts. Int. J. Mol. Med. 35, 161-168.   DOI