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Maxillary Sinus Floor Elevation Using BMP-2 and Nell-1 Gene-Modified Bone Marrow Stromal Cells and TCP in Rabbits

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Abstract

This study evaluated the synergistic osteogenic effect of bone morphogenetic protein-2 (BMP-2) and Nel-like molecule-1 (Nell-1) genes in a rabbit maxillary sinus floor elevation model. Bone marrow stromal cells (bMSCs) were cultured and transduced with AdEGFP, AdNell-1, AdBMP-2, or AdNell-1 + AdBMP-2 overexpression virus. These gene-modified autologous bMSCs were then combined with a β-tricalcium phosphate (β-TCP) granule scaffold and used to elevate the maxillary sinus floor in rabbits. bMSCs cotransduced with AdNell-1 + AdBMP-2 demonstrated a synergistic effect on osteogenic differentiation as detected by real-time PCR analysis on markers of runt-related transcription factor-2, osteocalcin, collagen type 1, alkaline phosphatase activity, and calcium deposits in vitro. As for maxillary sinus floor elevation in a rabbit model in vivo, AdNell-1 + AdBMP-2 gene–transduced autologeous bMSCs/β-TCP complex had the largest bone area and most mature bone structure among the groups, as detected by HE staining and immunohistochemistry at weeks 2 and 8 after implantation. Our data suggested that the BMP-2 and Nell-1 genes possessed a synergistic effect on osteogenic differentiation of bMSCs, while bMSCs modified with the BMP-2 and Nell-1 genes could promote new bone formation and maturation in the rabbit maxillary sinus model.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (30772431, 30973342), the Program for New Century Excellent Talents in University (NCET-08-0353), the Science and Technology Commission of Shanghai Municipality (08410706400, S30206, 0952nm04000, 10430710900, 10dz2211600, 10ZR1418100), the Shanghai Rising-Star Program (08QH14017), and the Shanghai Education Committee (07SG19).

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Authors and Affiliations

  1. Department of Oral and Maxillofacial Surgery, Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, People’s Republic of China

    Lunguo Xia, Yuanjin Xu & Zhiyuan Zhang

  2. Oral Bioengineering Lab, Shanghai Research Institute of Stomatology, Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai Key Laboratory of Stomatology, 639 Zhizaoju Road, Shanghai, 200011, People’s Republic of China

    Lunguo Xia, Qing Chang, Deliang Zeng, Wenjie Zhang, Xiuli Zhang, Zhiyuan Zhang & Xinquan Jiang

  3. Department of Oral Maxillofacial Surgery, Affiliated Hospital of Ningxia Medical University, Ningxia, 750004, People’s Republic of China

    Xiaojuan Sun

  4. Department of Prosthodontics, Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, People’s Republic of China

    Deliang Zeng, Wenjie Zhang & Xinquan Jiang

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  1. Lunguo Xia
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Correspondence to Zhiyuan Zhang or Xinquan Jiang.

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Xia, L., Xu, Y., Chang, Q. et al. Maxillary Sinus Floor Elevation Using BMP-2 and Nell-1 Gene-Modified Bone Marrow Stromal Cells and TCP in Rabbits. Calcif Tissue Int 89, 53–64 (2011). https://doi.org/10.1007/s00223-011-9493-1

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  • DOI: https://doi.org/10.1007/s00223-011-9493-1

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