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Scientific Articles   |    
Synergistic Effect of Bone Morphogenetic Proteins 2 and 7 by ex Vivo Gene Therapy in a Rat Spinal Fusion Model
Takashi Kaito, MD, PhD1; Jared Johnson, MD2; Jessica Ellerman, MD2; Haijun Tian, MD2; Mehmet Aydogan, MD2; Mongkol Chatsrinopkun, MD2; Stephanie Ngo, MPH2; Christine Choi, BS2; Jeffrey C. Wang, MD2
1 Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871 Japan. E-mail address: takashikaito@gmail.com
2 Department of Orthopaedic Surgery, University of California at Los Angeles, Box 956902, Los Angeles, CA 90095-1570
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Investigation performed at the Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan, and the Department of Orthopaedic Surgery, University of California at Los Angeles, Los Angeles, California



Disclosure: One or more of the authors received payments or services, either directly or indirectly (i.e., via his or her institution), from a third party in support of an aspect of this work. In addition, one or more of the authors, or his or her institution, has had a financial relationship, in the thirty-six months prior to submission of this work, with an entity in the biomedical arena that could be perceived to influence or have the potential to influence what is written in this work. No author has had any other relationships, or has engaged in any other activities, that could be perceived to influence or have the potential to influence what is written in this work. The complete Disclosures of Potential Conflicts of Interest submitted by authors are always provided with the online version of the article.

Copyright © 2013 by The Journal of Bone and Joint Surgery, Inc.
J Bone Joint Surg Am, 2013 Sep 04;95(17):1612-1619. doi: 10.2106/JBJS.L.01396
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Abstract

Background: 

Previous studies have suggested that the co-expression of two different bone morphogenetic protein (BMP) genes can result in the production of heterodimeric BMPs that may be more potent than homodimers. In this study, combined BMP-2 and BMP-7 gene transfer was performed ex vivo to compare the resulting new bone formation with that of single-BMP gene transfer in a rat spinal fusion model.

Methods: 

Forty-four athymic rats underwent posterolateral fusion at L4-L5 and were implanted with a collagen sponge containing human adipose-derived stem cells. Group A received untreated cells, and the remaining groups received cells transfected with various genes in a lentivirus vector. The transferred genes were GFP (green fluorescent protein) in Group B, BMP-2 in Group C, BMP-7 in Group D, and both BMP-2 and BMP-7 in Group E. In vitro production of BMP-2 and BMP−7 was quantified by means of an enzyme-linked immunosorbent assay (ELISA) specific to BMP-2 or BMP-7. Osseous fusion was quantified with use of radiography and microcomputed tomography.

Results: 

ELISA demonstrated that Group E, which was treated with both BMP-2 and BMP-7, produced less than one-fourth as much BMP as the groups treated with a single transfected BMP (Groups C and D). Radiographs showed that all of the spines in Groups C, D, and E appeared to be fused by eight weeks; the spines in Groups A and B showed minimal evidence of new bone formation. Measurements confirmed that the mean bone formation area was significantly greater in Groups C, D, and E compared with Groups A and B (p < 0.001). In addition, the bone formation area was significantly greater in Group E compared with Groups C and D (p < 0.001).

Conclusions: 

Combined BMP-2 and BMP-7 ex vivo gene transfer was found to be significantly more effective for inducing new bone formation compared with ex vivo gene transfer of an individual BMP in a rat spinal fusion model.

Clinical Relevance: 

Combined BMP-2 and BMP-7 therapy may lead to efficient bone regeneration.

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    References

    Accreditation Statement
    These activities have been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Academy of Orthopaedic Surgeons and The Journal of Bone and Joint Surgery, Inc. The American Academy of Orthopaedic Surgeons is accredited by the ACCME to provide continuing medical education for physicians.
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