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Amelogenin is phagocytized and induces changes in integrin configuration, gene expression and proliferation of cultured normal human dermal fibroblasts

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Abstract

Fibroblasts are central in wound healing by expressing important mediators and producing and remodelling extracellular matrix (ECM) components. This study aimed at elucidating possible mechanisms of action of the ECM protein amelogenin on normal human dermal fibroblasts (NHDF). Amelogenin at 100 and 1000 μg/ml increased binding of NHDF via several integrins, including αvβ3, αvβ5 and α5β1. Further, both surface interaction and cellular uptake of amelogenin by NHDF was observed using scanning and transmission electron microscopy. Gene microarray studies showed >8-fold up or down-regulation of genes, of which most are involved in cellular growth, migration and differentiation. The effect of amelogenin was exemplified by increased proliferation over 7 days. In conclusion, the beneficial effects of amelogenin on wound healing are possibly conducted by stimulating fibroblast signalling, proliferation and migration via integrin interactions. It is hypothesized that amelogenin stimulates wound healing by providing connective tissue cells with a temporary extracellular matrix.

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Acknowledgements

The authors would like to thank the members of the Electron Microscopy Unit at Sahlgrenska Academy, Göteborg, Sweden for the expert technical assistance during the electron microscopy studies. The support by the Swedish Research Council (grant K2006-73X-09495-16-3), Hjalmar Svensson Foundation, Mölnlycke Health Care AB and the Institute of Biomaterials and Cell Therapy (IBCT) (part of GöteborgBIO), is gratefully acknowledged.

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Authors and Affiliations

  1. Department of Biomaterials, Sahlgrenska Academy at University of Gothenburg, Box 412, 405 30, Göteborg, Sweden

    Sofia Almqvist, Maria Werthén, Anna Johansson & Peter Thomsen

  2. Institute of Biomaterials and Cell Therapy, Göteborg, Sweden

    Sofia Almqvist, Maria Werthén, Anna Johansson & Peter Thomsen

  3. Mölnlycke Health Care AB, Göteborg, Sweden

    Sofia Almqvist & Maria Werthén

  4. BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Göteborg, Sweden

    Anna Johansson & Peter Thomsen

  5. Department of Surgery K and Copenhagen Wound Healing Center, Bispebjerg Hospital, Copenhagen, Denmark

    Magnus S. Ågren

  6. Department of Biomaterials, Institute for Clinical Dentistry, University of Oslo, Oslo, Norway

    S. Petter Lyngstadaas

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  1. Sofia Almqvist
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  2. Maria Werthén
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  3. Anna Johansson
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  4. Magnus S. Ågren
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  6. S. Petter Lyngstadaas
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Correspondence to Sofia Almqvist.

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Almqvist, S., Werthén, M., Johansson, A. et al. Amelogenin is phagocytized and induces changes in integrin configuration, gene expression and proliferation of cultured normal human dermal fibroblasts. J Mater Sci: Mater Med 21, 947–954 (2010). https://doi.org/10.1007/s10856-009-3952-5

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  • DOI: https://doi.org/10.1007/s10856-009-3952-5

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