Gene therapy with human osteoprotegerin decreases callus remodeling with limited effects on biomechanical properties

Osteoprotegerin (OPG) is a naturally occurring protein, which prevents bone resorption by inhibition of osteoclastogenesis, function, and survival. Therefore, recombinant OPG may be an attractive drug in the treatment of chronic bone resorptive diseases such as osteoporosis. Gene therapy has the pot...

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Bibliographic Details
Published in:Bone (New York, N.Y.) N.Y.), 2005-12, Vol.37 (6), p.751-758
Main Authors: Ulrich-Vinther, Michael, Schwarz, Edward M., Pedersen, Finn S., Søballe, Kjeld, Andreassen, Troels T.
Format: Article
Language:English
Subjects:
AAV
Adeno-associated virus
Animals
Biological and medical sciences
Biomechanical Phenomena
Body Weight
Bone Remodeling
Bony Callus - cytology
Bony Callus - diagnostic imaging
Bony Callus - physiology
Female
Fracture healing
Fractures, Bone - pathology
Fractures, Bone - therapy
Fundamental and applied biological sciences. Psychology
Gene therapy
Genetic Therapy
Glycoproteins - genetics
Humans
Injuries of the limb. Injuries of the spine
Medical sciences
Osteoprotegerin
Radiography
Rats
Rats, Wistar
Receptors, Cytoplasmic and Nuclear - genetics
Receptors, Tumor Necrosis Factor - genetics
Tibia - cytology
Tibia - diagnostic imaging
Tibia - injuries
Traumas. Diseases due to physical agents
Vertebrates: anatomy and physiology, studies on body, several organs or systems
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Summary:Osteoprotegerin (OPG) is a naturally occurring protein, which prevents bone resorption by inhibition of osteoclastogenesis, function, and survival. Therefore, recombinant OPG may be an attractive drug in the treatment of chronic bone resorptive diseases such as osteoporosis. Gene therapy has the potential to achieve long-term treatment by delivering genes of anti-resorptive proteins to the recipient. The effects of OPG gene therapy on fracture healing have not been described previously. The influence of OPG gene therapy on callus formation, callus tissue structural strength, apparent material properties, and histology of tibia fractures in rats was investigated after 3 weeks and 8 weeks of healing. Intramuscular administration of adeno-associated virus (AAV) vector-mediated OPG resulted in increased levels of OPG in serum of approximately 100 ng/ml throughout the study period. Control animals with fractures received transduction with an AAV reporter gene construct (AAV-enhanced green fluorescent protein (eGFP)), and in this group serum OPG levels remained at baseline (
ISSN:8756-3282
1873-2763
DOI:10.1016/j.bone.2005.07.021