BMP-14 gene therapy increases tendon tensile strength in a rat model of Achilles tendon injury.
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.


CONCLUSIONS
The results of this animal study suggest that gene therapy with BMPs may improve the capacity of injured musculoskeletal tissue to heal.
Bolt
Patrick
P
Section of Orthopaedic Surgery and Rehabilitation Medicine, Department of Surgery, University of Chicago Medical Center, 5841 South Maryland Avenue, MC 3079, Chicago, IL 60637, USA.
Clerk
Avnish Neil
AN
Luu
Hue H
HH
Kang
Quan
Q
Kummer
Jennifer L
JL
Deng
Zhong-Liang
ZL
Olson
Kirstina
K
Primus
Frank
F
Montag
Anthony G
AG
He
Tong-Chuan
TC
Haydon
Rex C
RC
Toolan
Brian C
BC
D000125:Achilles Tendon / Q000293:injuries* / Q000503:physiopathology; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D049452:Green Fluorescent Proteins; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013718:Tensile Strength / Q000187:drug effects*; D014945:Wound Healing / Q000187:drug effects*
D019485:Bone Morphogenetic Proteins; D049452:Green Fluorescent Proteins