The Journal of Bone and Joint Surgery (American). 2007;89:1315-1320.
doi:10.2106/JBJS.F.00257
© 2007 The Journal of Bone and Joint Surgery, Inc.
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BMP-14 Gene Therapy Increases Tendon Tensile Strength in a Rat Model of Achilles Tendon Injury

Patrick Bolt, MD1, Avnish Neil Clerk, MD1, Hue H. Luu, MD1, Quan Kang, MD1, Jennifer L. Kummer, MD1, Zhong-Liang Deng, MD, PhD1, Kirstina Olson, MD1, Frank Primus, BS1, Anthony G. Montag, MD1, Tong-Chuan He, MD, PhD1, Rex C. Haydon, MD, PhD1 and Brian C. Toolan, MD1

1 Section of Orthopaedic Surgery and Rehabilitation Medicine, Department of Surgery, University of Chicago Medical Center, 5841 South Maryland Avenue, MC 3079, Chicago, IL 60637. E-mail address for B.C. Toolan: btoolan{at}surgery.bsd.uchicago.edu

Investigation performed at the Section of Orthopaedic Surgery and Rehabilitation Medicine, Department of Surgery, University of Chicago Medical Center, Chicago, Illinois

Disclosure: In support of their research for or preparation of this work, one or more of the authors received, in any one year, outside funding or grants of less than $10,000 from the Orthopaedic Research and Education Foundation, the American Orthopaedic Foot and Ankle Society, and the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases. Neither they nor a member of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which the authors, or a member of their immediate families, are affiliated or associated.

NOTE: The authors thank Dezheng Huo of the Department of Health Studies for his expert assistance with the statistical analysis of the samples.

Background: Molecular and cellular-based enhancements of healing combined with conventional methods may yield better outcomes after the surgical management of tendon injury. We examined the histological and biomechanical effects of adenovirus-mediated transgene expression of bone morphogenetic protein-14 (BMP-14) on healing in a rat Achilles tendon laceration model. Specifically, we hypothesized that this delivery system for gene therapy would hasten the restoration of the normal histological appearance and tensile strength of a surgically repaired tendon.

Methods: The right Achilles tendon of ninety male Sprague-Dawley rats was transected, repaired, and immediately infected with adenovirus expressing either the gene for green fluorescent protein (AdGFP) or the gene for human BMP-14 and green fluorescent protein (AdBMP-14). A sham control group received no viral-mediated infection after repair. Animals from each of the three groups were killed at one, two, and three weeks after surgery. The retrieved tendons were inspected, examined under light and fluorescent microscopy, and tested to determine their tensile strength.

Results: Tendons transduced with BMP-14 exhibited less visible gapping, a greater number of neotenocytes at the site of healing, and 70% greater tensile strength than did either those transduced with GFP or the sham controls at two weeks after repair. Histological examination revealed no inflammatory response to the adenovirus in tendons transduced with BMP-14 or GFP. No ectopic bone or cartilage formed in the tendons transduced with BMP-14.

Conclusions: Adenovirus-mediated gene therapy with BMP-14 expedites tendon-healing in this animal model. No adverse immunological response to the adenoviral vector was detected in the host tissue, and the local production of BMP-14 did not induce unwelcome bone or cartilage formation within the healing tendon.

Clinical Relevance: The results of this animal study suggest that gene therapy with BMPs may improve the capacity of injured musculoskeletal tissue to heal.


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Letters to the Editor:

Read all Letters to the Editor

BMP-14 gene transfer into rat Achilles tendon
Markus Rickert, M.D., Ph.D
JBJS Online, 31 Jul 2007 [Full text]
Dr. Toolan et al. respond to Dr. Rickert.
Brian C. Toolan, M.D., et al.
JBJS Online, 31 Jul 2007 [Full text]