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Exposure to transforming growth factor-β1 after basic fibroblast growth factor promotes the fibroblastic differentiation of human periodontal ligament stem/progenitor cell lines

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Abstract

Basic fibroblast growth factor (bFGF) is a cytokine that promotes the regeneration of the periodontium, the specialized tissues supporting the teeth. bFGF, does not, however, induce the synthesis of smooth muscle actin alpha 2 (ACTA2), type I collagen (COL1), or COL3, which are principal molecules in periodontal ligament (PDL) tissue, a component of the periodontium. We have suggested the feasibility of using transforming growth factor-β1 (TGFβ1) to induce fibroblastic differentiation of PDL stem/progenitor cells (PDLSCs). Here, we investigated the effect of the subsequent application of TGFβ1 after bFGF (bFGF/TGFβ1) on the differentiation of PDLSCs into fibroblastic cells. We first confirmed the expression of bFGF and TGFβ1 in rat PDL tissue and primary human PDL cells. Receptors for both bFGF and TGFβ1 were expressed in the human PDLSC lines 1-11 and 1-17. Exposure to bFGF for 2 days promoted vascular endothelial growth factor gene and protein expression in both cell lines and down-regulated the expression of ACTA2, COL1, and COL3 mRNA in both cell lines and the gene fibrillin 1 (FBN1) in cell line 1-11 alone. Furthermore, bFGF stimulated cell proliferation of these cell lines and significantly increased the number of cells in phase G2/M in the cell lines. Exposure to TGFβ1 for 2 days induced gene expression of ACTA2 and COL1 in both cell lines and FBN1 in cell line 1-11 alone. BFGF/TGFβ1 treatment significantly up-regulated ACTA2, COL1, and FBN1 expression as compared with the group treated with bFGF alone or the untreated control. This method might thus be useful for accelerating the generation and regeneration of functional periodontium.

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Abbreviations

ACTA2:

Smooth muscle actin alpha 2

bFGF:

Basic fibroblast growth factor

COL1:

Type I collagen

COL3:

Type III collagen

DAPI:

4,6-Diamidino-2-phenylindole

FBN1:

Fibrillin 1

FGFR:

Fibroblast growth factor receptor

HPDLC:

Human periodontal ligament cell

PDL:

Periodontal ligament

PDLSC:

Periodontal ligament stem/progenitor cell

TGFβ1:

Transforming growth factor-β1

TGFBR:

Transforming growth factor-β receptor

VEGF:

Vascular endothelial growth factor

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Acknowledgments

We thank Drs. Hasegawa and Yuda for their great support in the preparation of this work.

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Authors and Affiliations

  1. Department of Endodontology and Operative Dentistry, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Kiyomi Kono, Atsushi Tomokiyo, Naohide Yamamoto, Satoshi Monnouchi, Yoko Teramatsu, Sayuri Hamano, Katsuaki Koori & Akifumi Akamine

  2. Department of Endodontology, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Hidefumi Maeda, Naohisa Wada & Akifumi Akamine

  3. Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, 565-0871, Japan

    Shinsuke Fujii

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  1. Kiyomi Kono
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  2. Hidefumi Maeda
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  3. Shinsuke Fujii
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  4. Atsushi Tomokiyo
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  11. Akifumi Akamine
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Correspondence to Hidefumi Maeda.

Additional information

This work was financially supported by Grants-in-Aid for Scientific Research (Project nos. 22390359, 23659890, 23689077, 24390426, 24659848, and 24792028) from the Japan Society for the Promotion of Science.

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Kono, K., Maeda, H., Fujii, S. et al. Exposure to transforming growth factor-β1 after basic fibroblast growth factor promotes the fibroblastic differentiation of human periodontal ligament stem/progenitor cell lines. Cell Tissue Res 352, 249–263 (2013). https://doi.org/10.1007/s00441-012-1543-0

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  • DOI: https://doi.org/10.1007/s00441-012-1543-0

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