Osteogenic gene regulation and relative acceleration of healing by adenoviral-mediated transfer of human BMP-2 or -6 in equine osteotomy and ostectomy models.
Abstract: This study evaluated healing of equine metatarsal osteotomies and ostectomies in response to percutaneous injection of adenoviral (Ad) bone morphogenetic protein (BMP)-2, Ad-BMP-6, or beta-galactosidase protein vector control (Ad-LacZ) administered 14 days after surgery. Radiographic and quantitative computed tomographic assessment of bone formation indicated greater and earlier mineralized callus in both the osteotomies and ostectomies of the metatarsi injected with Ad-BMP-2 or Ad-BMP-6. Peak torque to failure and torsional stiffness were greater in osteotomies treated with Ad-BMP-2 than Ad-BMP-6, and both Ad-BMP-2- and Ad-BMP-6-treated osteotomies were greater than Ad-LacZ or untreated osteotomies. Gene expression of ostectomy mineralized callus 8 weeks after surgery indicated upregulation of genes related to osteogenesis compared to intact metatarsal bone. Expression of transforming growth factor beta-1, cathepsin H, and gelsolin-like capping protein were greater in Ad-BMP-2- and Ad-BMP-6-treated callus compared to Ad-LacZ-treated or untreated callus. Evidence of tissue biodistribution of adenovirus in distant organs was not identified by quantitative PCR, despite increased serum antiadenoviral vector antibody. This study demonstrated a greater relative potency of Ad-BMP-2 over Ad-BMP-6 in accelerating osteotomy healing when administered in this regimen, although both genes were effective at increasing bone at both osteotomy and ostectomy sites.
Publication Date: 2008-02-05 PubMed ID: 18241059DOI: 10.1002/jor.20585Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research essentially investigates how osteotomy and ostectomy healing in horses can be accelerated using adenoviral bone morphogenetic proteins (Ad-BMP)-2 and Ad-BMP-6. It found that both these proteins could enhance bone regeneration, with Ad-BMP-2 showing slightly better results.
Objective and Methodology
- The primary purpose of the study was to examine the healing process of equine metatarsal osteotomies and ostectomies which have been subjected to an injection of adenoviral (Ad) bone morphogenetic proteins (BMP)-2 and Ad-BMP-6.
- This was negotiated by administering these proteins percutaneously (through the skin) 14 days post-surgery.
- The effectiveness of these proteins was compared to a control group injected with a beta-galactosidase protein vector (Ad-LacZ).
- The research employed radiographic and quantitative computed tomographic assessments to gauge bone formation in response to these treatments.
Findings of the Study
- According to the results of the assessments, injection with Ad-BMP-2 or Ad-BMP-6 resulted in greater and faster mineralized callus (bone healing tissue) formation in both the osteotomies and ostectomies.
- Osteotomies treated with Ad-BMP-2 had greater peak torque to failure and torsional stiffness compared to those treated with Ad-BMP-6.
- Both Ad-BMP-2 and Ad-BMP-6 proved superior to Ad-LacZ in these metrics, and also compared to untreated osteotomies.
Post-Surgery Gene Expression
- The research also analyzed ostectomy mineralized callus gene expression 8 weeks after surgery.
- The gene expression indicated increased upregulation of genes related to osteogenesis compared to intact metatarsal bone.
- Expression of transforming growth factor beta-1, cathepsin H, and gelsolin-like capping protein was found to be greater in Ad-BMP-2 and Ad-BMP-6 treated callus as opposed to those treated with Ad-LacZ or those untreated.
Additional Findings
- Despite an increase in serum antiadenoviral vector antibody, there was no detection of adenovirus tissue biodistribution in distant organs through quantitative PCR.
- The research thus also suggests a minimal adverse effect from the use of adenovirus as a vector for bone regeneration.
Conclusion
- The study identified both Ad-BMP-2 and Ad-BMP-6 as effective in accelerating healing in osteotomy and ostectomy sites.
- However, Ad-BMP-2 had greater relative potency in encouraging osteotomy healing when administered in this regimen.
Cite This Article
APA
Ishihara A, Shields KM, Litsky AS, Mattoon JS, Weisbrode SE, Bartlett JS, Bertone AL.
(2008).
Osteogenic gene regulation and relative acceleration of healing by adenoviral-mediated transfer of human BMP-2 or -6 in equine osteotomy and ostectomy models.
J Orthop Res, 26(6), 764-771.
https://doi.org/10.1002/jor.20585 Publication
Researcher Affiliations
- Comparative Orthopedic Research Laboratories, Department of Veterinary Clinical Sciences, The Ohio State University, 601 Tharp Street, Columbus, Ohio 43210, USA.
MeSH Terms
- Adenoviridae / genetics
- Animals
- Biomechanical Phenomena
- Bone Morphogenetic Protein 2
- Bone Morphogenetic Protein 6
- Bone Morphogenetic Proteins / genetics
- Bony Callus / diagnostic imaging
- Bony Callus / physiopathology
- Disease Models, Animal
- Fracture Healing / genetics
- Fractures, Bone / diagnostic imaging
- Fractures, Bone / physiopathology
- Fractures, Bone / therapy
- Gene Expression Regulation
- Gene Transfer Techniques
- Genetic Therapy / methods
- Horses
- Humans
- Lac Operon
- Metatarsal Bones / diagnostic imaging
- Metatarsal Bones / physiology
- Oligonucleotide Array Sequence Analysis
- Osteogenesis / genetics
- Osteotomy
- Tomography, X-Ray Computed
- Torque
- Torsion, Mechanical
- Transforming Growth Factor beta / genetics
Citations
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