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Influence of bone morphogenetic protein-2 on spiral ganglion neurite growth in vitro

  • Otology
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Abstract

Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a growth factor of the transforming growth factor-β superfamily. Members of this protein family are involved in the development of various mammalian tissues, including the inner ear. As their notations indicate, they also have well-known effects on bone formation and regeneration. In this study, we examined the influence of rhBMP-2 on spiral ganglion (SG) neurite growth in vitro and showed the presence of its most preferred receptor BMPR-IB in spiral ganglion cells both in vitro and in vivo. SG explants of postnatal day 4 rats were analysed for neurite length and number after organotypical cell culture for 72 h, fixation and immunolabeling. Different concentrations of rhBMP-2 were used in a serum-free culture media. Neurite growth was compared with control groups that lacked stimulative effects; with neutrophin-3 (NT-3), which is a well-established positive stimulus on neurite length and number; and with combinations of these parameters. The results display that neurite number and total neurite length per explant in particular concentrations of rhBMP-2 increased by a maximum factor of two, while the mean neurite length was not affected. NT-3 demonstrated a much more potent effect, delivering a maximum increase of a factor of five. Furthermore, a combination of both growth factors shows a predominant effect on NT-3. Immunohistological detection of BMPR-IB was successful both in cell culture explants and in paraffin-embedded sections of animals of different ages. The results show that rhBMP-2 is, among other growth factors, a positive stimulus for SG neurite growth in vitro. Most growth factors are unstable and cannot be attached to surfaces without loss of their biological function. In contrast, rhBMP-2 can be attached to metal surfaces without loss of activity. Our findings suggest in vivo studies and a future clinical application of rhBMP-2 in cochlear implant technology to improve the tissue/electrode interface.

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Acknowledgments

The authors thank Mrs. Susanne Kanabey for technical assistance in histology and immunolabeling and Patrick Hsu for his comments on the manuscript.

Conflict of interest statement

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Otorhinolaryngology-Head and Neck Surgery, St. Elisabeth-Hospital Bochum, Ruhr-University of Bochum, Bleichstr. 15, 44787, Bochum, Germany

    Stefan Volkenstein, D. Brors, S. Hansen, A. Minovi, S. Dazert & A. Neumann

  2. Institute of Physiological Chemistry, University of Essen, Essen, Germany

    M. Laub & H. P. Jennissen

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  1. Stefan Volkenstein
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  2. D. Brors
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Correspondence to Stefan Volkenstein.

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Volkenstein, S., Brors, D., Hansen, S. et al. Influence of bone morphogenetic protein-2 on spiral ganglion neurite growth in vitro. Eur Arch Otorhinolaryngol 266, 1381–1389 (2009). https://doi.org/10.1007/s00405-009-0930-y

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  • DOI: https://doi.org/10.1007/s00405-009-0930-y

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