Class

Article

College

College of Agriculture and Applied Sciences

Department

Animal, Dairy, and Veterinary Sciences Department

Presentation Type

Oral Presentation

Abstract

The effect of Timp-3 Transgene delivered using a viral vector on osteoarthritis in an ovine mode Crystal G. Collier, Peter Welsh, Kate C. Parkinson, Anisa Samhouri, McKenna R. Walters, Jeffrey B. Maso Department of Animal, Dairy, and Veterinary Sciences, School of Veterinary Medicine, Utah State University, Logan, Utah The aim of our current research is to investigate a study of the security and remedial potential of a Timp-3 transgene delivered by a recombinant adeno-associated viral vector (rAAV) for prevention of osteoarthritis (OA). There is radiographic evidence in more than 80% of those over the age of 65, particularly in post-menopausal women. To improve the study of this disease, a large animal model physiologically similar to human is needed for closely applicable research. Two of the most common surgical methods of induction include the ovariectomy (OVX) and cranial cruciate ligament desmotomy (CCLD). An additional approach to increasing severity of OA is forced exercise. In our design, we combine these two surgical procedures (OVX, n=7 and CCLD, n=8) and oblique-angle forced exercise to create and osteoarthritic environment where gene therapy can be analyzed. In an OA environment, degradative enzymes known as matrix metalloproteinases play a central role. In a pilot study, we established that tissue inhibitor of metalloproteinase-3 gene (Timp-3) cut off these destructive enzymes in turn diminishing break down of cartilage tissues. Our current study targets the up-regulation of Timp-3 protein in situ by the addition of a Timp-3 transgene delivered by a rAAV directly into the stifle of the surgically-altered sheep. A 14-week routine of oblique-angle forced exercise was then accomplished in all subjects and subjects were then collected for analysis. Preliminary analysis of digital radiographs suggest a significant effect from the Timp-3 transgene in both models in toward the reduction of osteophytosis, the most commonly used measure of OA progression. By study of this process, we aspire to develop an effective preventative measure to be used by those suffering from OA.

Location

Room 155

Start Date

4-10-2019 12:00 PM

End Date

4-10-2019 1:15 PM

Included in

Life Sciences Commons

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Apr 10th, 12:00 PM Apr 10th, 1:15 PM

Using rAAV-TIMP3 Vectors for the Improvement of Osteoarthritis in an Ovine Model

Room 155

The effect of Timp-3 Transgene delivered using a viral vector on osteoarthritis in an ovine mode Crystal G. Collier, Peter Welsh, Kate C. Parkinson, Anisa Samhouri, McKenna R. Walters, Jeffrey B. Maso Department of Animal, Dairy, and Veterinary Sciences, School of Veterinary Medicine, Utah State University, Logan, Utah The aim of our current research is to investigate a study of the security and remedial potential of a Timp-3 transgene delivered by a recombinant adeno-associated viral vector (rAAV) for prevention of osteoarthritis (OA). There is radiographic evidence in more than 80% of those over the age of 65, particularly in post-menopausal women. To improve the study of this disease, a large animal model physiologically similar to human is needed for closely applicable research. Two of the most common surgical methods of induction include the ovariectomy (OVX) and cranial cruciate ligament desmotomy (CCLD). An additional approach to increasing severity of OA is forced exercise. In our design, we combine these two surgical procedures (OVX, n=7 and CCLD, n=8) and oblique-angle forced exercise to create and osteoarthritic environment where gene therapy can be analyzed. In an OA environment, degradative enzymes known as matrix metalloproteinases play a central role. In a pilot study, we established that tissue inhibitor of metalloproteinase-3 gene (Timp-3) cut off these destructive enzymes in turn diminishing break down of cartilage tissues. Our current study targets the up-regulation of Timp-3 protein in situ by the addition of a Timp-3 transgene delivered by a rAAV directly into the stifle of the surgically-altered sheep. A 14-week routine of oblique-angle forced exercise was then accomplished in all subjects and subjects were then collected for analysis. Preliminary analysis of digital radiographs suggest a significant effect from the Timp-3 transgene in both models in toward the reduction of osteophytosis, the most commonly used measure of OA progression. By study of this process, we aspire to develop an effective preventative measure to be used by those suffering from OA.