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Secretoneurin, a Neuropeptide, Enhances Bone Regeneration in a Mouse Calvarial Bone Defect Model

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Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

Background:

This study investigates the effects of a neuropeptide, secretoneurin (SN), on bone regeneration in an experimental mouse model.

Methods:

The effects of SN on cell proliferation, osteoblast marker genes expression, and mineralization were evaluated using the CCK-8 assay, quantitative reverse transcriptase polymerase chain reaction (RT-PCR), and alizarin red S staining, respectively. To examine the effects of SN on bone regeneration in vivo, bone defects were created in the calvaria of ICR mice, and 0.5 or 1 µg/ml SN was applied. New bone formation was analyzed by micro-computed tomography (micro-CT) and histology. New blood vessel formation was assessed by CD34 immunohistochemistry.

Results:

SN had no significant effect on proliferation and mineralization of MC3T3-E1 cells. However, SN partially induced the gene expression of osteoblast differentiation markers such as runt-related transcription factor 2, alkaline phosphatase, collagen type I alpha 1, and osteopontin. A significant increase of bone regeneration was observed in SN treated calvarial defects. The bone volume (BV), BV/tissue volume, trabecular thickness and trabecular number values were significantly increased in the collagen sponge plus 0.5 or 1 µg/ml SN group (p < 0.01) compared with the control group. Histologic analysis also revealed increased new bone formation in the SN-treated groups. Immunohistochemical staining of CD34 showed that the SN-treated groups contained more blood vessels compared with control in the calvarial defect area.

Conclusion:

SN increases new bone and blood vessel formation in a calvarial defect site. This study suggests that SN may enhance new bone formation through its potent angiogenic activity.

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Acknowledgements

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean Government (MSIT) (NRF-2017R1A5A2015391), and the Bio & Medical Technology Development Program of the NRF, which was funded by the Korean Government (MSIT) (2017M3A9E4047244).

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Authors and Affiliations

  1. Department of Oral Pathology and Regenerative Medicine, School of Dentistry, Kyungpook National University, 2177 Dalgubeol-daero, Jung-gu, Daegu, 41940, Republic of Korea

    Freshet Assefa, Jiwon Lim, Ju-Ang Kim, Soomin Lim, Sang-Hyeon Nam & Eui Kyun Park

  2. Cell & Matrix Research Institute, Kyungpook National University, Daegu, 41944, Republic of Korea

    Hye Jung Ihn

  3. Department of Oral Anatomy and Neurobiology, School of Dentistry, Kyungpook National University, Daegu, 41940, South Korea

    Yong Chul Bae

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  1. Freshet Assefa
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Contributions

F. A. and E. K. P. designed the research and wrote the manuscript; F. A., H. J. I., J. A. K., J. L., S. L., and S.‐H. N. performed the experiments and analyzed the results; F. A., H. J. I., Y. C. B. and E. K. P. analyzed the data and revised the manuscript; and E. K. P. supervised the project.

Corresponding author

Correspondence to Eui Kyun Park.

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The authors have no financial conflicts of interest.

Ethical statement

Animal experiments were performed in accordance with the guidelines approved by Kyungpook National University (No. 2018–0153).

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Assefa, F., Lim, J., Kim, JA. et al. Secretoneurin, a Neuropeptide, Enhances Bone Regeneration in a Mouse Calvarial Bone Defect Model. Tissue Eng Regen Med 18, 315–324 (2021). https://doi.org/10.1007/s13770-020-00304-1

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  • DOI: https://doi.org/10.1007/s13770-020-00304-1

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