Influence of bone morphogenetic protein-2 on spiral ganglion neurite growth in vitro.
Recombinant human bone morphogenetic protein-2 (rhBMP-2) is a growth factor of the transforming growth factor-beta 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.
Volkenstein
Stefan
S
Department of Otorhinolaryngology-Head and Neck Surgery, St. Elisabeth-Hospital Bochum, Ruhr-University of Bochum, Bleichstr. 15, 44787, Bochum, Germany. stefan.volkenstein@rub.de
Brors
D
D
Hansen
S
S
Minovi
A
A
Laub
M
M
Jennissen
H P
HP
Dazert
S
S
Neumann
A
A
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D016895:Culture Media, Serum-Free; D016501:Neurites / Q000187:drug effects / Q000502:physiology*; D055495:Neurogenesis / Q000187:drug effects*; D020933:Neurotrophin 3 / Q000494:pharmacology; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology*; D013136:Spiral Ganglion / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D016895:Culture Media, Serum-Free; D020933:Neurotrophin 3; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D052005:Bone Morphogenetic Protein Receptors, Type I