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Effects of VEGF and FGF-2 on proliferation and differentiation of human periodontal ligament stem cells

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Abstract

Human periodontal ligament stem cells (PDLSCs) from extracted third molar teeth are a type of adult stem cell originating from dental tissue. PDLSCs are known to have a self-renewal capacity and multi-lineage differentiation potential. Vascular endothelial growth factor (VEGF), an angiogenic/vasculogenic factor, has been shown to stimulate endothelial cell mitogenesis and cell migration. Another growth factor, fibroblast growth factor-2 (FGF-2), a mitogenic factor, enhances osteogenesis in mesenchymal stem cells (MSCs). This study examines the effects of VEGF and FGF-2 on PDLSCs in vitro and in vivo compared with those on bone marrow stem cells (BMSCs) as a positive control. Treatment of PDLSCs with VEGF increases the accumulation of calcium nodules, alkaline phosphatase (ALP) activity and the formation of hard tissue and up-regulates the mRNA level of runt-related transcription factor 2 (Runx2). In contrast, FGF-2 enhances the proliferation of PDLSCs in vitro in cell culture, where it significantly decreases calcium accumulation and ALP activity and down-regulates the expression of osteogenic gene markers (i.e., Runx2, ALP, type I collagen) involved in osteogenic induction. We have also transplanted PDLSCs with hydroxyapatite/tricalcium phosphate particles (HA/TCP) as carriers for each factor (VEGF, FGF-2) into nude mice and, after 8 weeks, observed the in vivo formation of hard tissue at the dorsal surface. Based on our results, we suggest that VEGF has positive effects on odonto-/osteogenic differentiation in vitro and on the formation of mineralized structure in vivo. FGF-2 might be a powerful promoter of the proliferation of progenitor cells in hard tissue regeneration but exogenous FGF-2 might inhibit terminal differentiation.

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Acknowledgement

We thank Prof. J.C. Park (Department of Oral Histology-Developmental Biology, Seoul National University, Korea) for providing antibodies to BSP and DSP.

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Authors and Affiliations

  1. Biotooth Engineering Lab, Department of Oral and Maxillofacial Surgery, School of Dentistry, BK21, Craniomaxillofacial Life Science, Dental Research Institute, Seoul National University, Seoul, Republic of Korea

    Joo-Hee Lee, Soyoun Um & Byoung Moo Seo

  2. Department of Biochemistry, School of Medicine, Inha University, Incheon, Republic of Korea

    Jun-Hyeog Jang

  3. Department of Oral and Maxillofacial Surgery, Seoul National University School of Dentistry, 28 Yongun-dong Jongno-gu, Seoul, Republic of Korea

    Byoung Moo Seo

Authors
  1. Joo-Hee Lee
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  2. Soyoun Um
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  3. Jun-Hyeog Jang
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  4. Byoung Moo Seo
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Corresponding author

Correspondence to Byoung Moo Seo.

Additional information

This research was supported by a grant of the Korea Healthcare Technology R&D Project, Ministry of Health, Welfare & Family Affairs, Republic of Korea (A085021).

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Supplementary Fig. 1

Bone sialoprotein (BSP) and dentin sialoprotein (DSP) immunohistochemistry. At 8 weeks after transplantation, BSP and DSP were stained. The expression of BSP was detected in both PDLSCs (a) and BMSCs (c)-derived hard tissue. On the other hand, the expressions of DSP was negative in both groups (b, d). Each control were stained with preimmune serum (H hard tissue formation, HA hydroxyapatite/tricalcium phosphate particles. Magnification ×20. Bars 100 μm. (JPEG 101 kb)

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Lee, JH., Um, S., Jang, JH. et al. Effects of VEGF and FGF-2 on proliferation and differentiation of human periodontal ligament stem cells. Cell Tissue Res 348, 475–484 (2012). https://doi.org/10.1007/s00441-012-1392-x

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  • DOI: https://doi.org/10.1007/s00441-012-1392-x

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