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Comparison of the effects of recombinant human bone morphogenetic protein-2 and -9 on bone formation in rat calvarial critical-size defects

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Abstract

Objectives

Among bone morphogenetic protein (BMP) family members, BMP-2 and BMP-9 have demonstrated potent osteoinductive potential. However, in vivo differences in their potential for bone regeneration remain unclear. The present study aimed to compare the effects of recombinant human (rh) BMP-2 and rhBMP-9 on bone formation in rat calvarial critical-size defects (CSD).

Materials and methods

Twenty-eight Wistar rats surgically received two calvarial defects bilaterally in each parietal bone. Defects (n = 56) were allocated into four groups: absorbable collagen sponge (ACS) alone, rhBMP-2 with ACS (rhBMP-2/ACS), rhBMP-9/ACS, or sham surgery (control), on the condition that the treatments of rhBMP-2/ACS and rhBMP-9/ACS, or the same treatments were not included in the same animal. Animals were sacrificed at 2 and 8 weeks post-surgery. The calvarial defects were analyzed for bone volume (BV) by micro-computed tomography and for percentages of defect closure (DC/DL), newly formed bone area (NBA/TA), bone marrow area (BMA/NBA), adipose tissue area (ATA/NBA), central bone height (CBH), and marginal bone height (MBH) by histomorphometric analysis.

Results

The BV in the rhBMP-2/ACS group (5.44 ± 3.65 mm3, n = 7) was greater than the other groups at 2 weeks post-surgery, and the rhBMP-2/ACS and rhBMP-9/ACS groups (18.17 ± 2.51 and 16.30 ± 2.46 mm3, n = 7, respectively) demonstrated significantly greater amounts of BV compared with the control and ACS groups (6.02 ± 2.90 and 9.30 ± 2.75 mm3, n = 7, respectively) at 8 weeks post-surgery. The rhBMP-2/ACS and rhBMP-9/ACS groups significantly induced new bone formation compared to the control and ACS groups at 8 weeks post-surgery. However, there were no statistically significant differences found between the rhBMP-2/ACS and rhBMP-9/ACS groups in any of the histomorphometric parameters. The ATA/NBA in the rhBMP-2/ACS group (9.24 ± 3.72%, n = 7) was the highest among the treatment groups at 8 weeks post-surgery.

Conclusions

Within the limits of this study, it can be concluded that rhBMP-2/ACS induced a slight early increase in new bone formation at 2 weeks and that rhBMP-9/ACS provided comparable new bone formation to rhBMP-2/ACS with less adipose tissues after a healing period of 8 weeks in rat CSD.

Clinical relevance

RhBMP-9/ACS treatment provided new bone formation with less adipose tissues compared with rhBMP-2/ACS.

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Acknowledgements

The authors are grateful to Dr. Chihaya Koriyama, Department of Epidemiology and Preventive Medicine at Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan, for her assistance in performing the statistical analysis.

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Authors and Affiliations

  1. Department of Periodontology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan

    Toshiaki Nakamura, Yoshinori Shirakata, Yukiya Shinohara, Kozue Hasegawa-Nakamura & Kazuyuki Noguchi

  2. Department of Periodontology, Nova Southeastern University, Fort Lauderdale, FL, USA

    Richard J. Miron

  3. Department of Cranio-Maxillofacial Surgery, Bern University Hospital, Inselspital, Bern, Switzerland

    Masako Fujioka-Kobayashi

  4. Department of Oral Surgery, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan

    Masako Fujioka-Kobayashi

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  1. Toshiaki Nakamura
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  2. Yoshinori Shirakata
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  3. Yukiya Shinohara
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  4. Richard J. Miron
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  5. Kozue Hasegawa-Nakamura
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  6. Masako Fujioka-Kobayashi
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  7. Kazuyuki Noguchi
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Corresponding author

Correspondence to Kazuyuki Noguchi.

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Conflict of interest

The authors declare that they have no conflicts of interests.

Funding

This study was supported by Grants-in-Aid for Scientific Research (B) (No.24792147) and (C) (No.26462972) from the Japan Society for the Promotion of Science (JSPS).

Ethical approval

All animal experimental protocols and procedures were approved by the Ethical Committee of the Animal Research Center of Kagoshima University, Japan (D14023).

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Informed consent was not required in this study.

Additional information

Toshiaki Nakamura and Yoshinori Shirakata equally contributed to this work.

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Nakamura, T., Shirakata, Y., Shinohara, Y. et al. Comparison of the effects of recombinant human bone morphogenetic protein-2 and -9 on bone formation in rat calvarial critical-size defects. Clin Oral Invest 21, 2671–2679 (2017). https://doi.org/10.1007/s00784-017-2069-3

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