Title of Oral/Poster Presentation

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

Class

Article

College

College of Agriculture and Applied Sciences

Faculty Mentor

Jeffrey Mason

Presentation Type

Oral Presentation

Abstract

Osteoarthritis is the most common joint disorder in the United States. It becomes most prevalent in adults reaching 60+ years of age and causes discomfort, decreased mobility and in some cases even excruciating pain. A large animal model for osteoarthritis is necessary for furthering the research and solution potential for this ubiquitous disease. Using an ovine model proves an effective technique in characterizing joint issues and with a demonstrated method of inducing the osteoarthritis over a period of months, not years, we can make hefty strides in furthering understanding of the disease. Our method involves two groups of surgically altered, mature ewes. One half undergoing ovariectomies and the other half a CCLD (Cranial Cruciate Ligament Desotomy). With one type of these surgeries and the use of oblique angle forced exercise over a period of approximately 4 months, significant effects of osteoarthritis will be observed. In the biological processes of osteoarthritis, the enzymes responsible for the degeneration of aggrecan, a key proteoglycan of cartilage, are upregulated in the animal. Inside the proteoglycan protein, the aggrecanases cause deterioration of the glycosaminoglycans. The regular maintainers of this enzyme’s activity are known as Tissue Inhibitor of Metalloproteinases (TIMPs). They keep the enzyme activity standard, however, a larger production of aggrecanases was noted in the osteoarthritis influenced cartilage. This study focuses on the up-regulating of full-length TIMP-3 protein signaling in situ using the introduction of a TIMP-3 transgene in a monolayer-cell/cartilage-tissue co-culture model. It is hypothesized that, in situ, up-regulation of cell-produced, full length TIMP-3 protein would decrease proteoglycan degradation. Understanding and utilizing these methods and research is hoped to make way for a new and better solution for the many affected by this disease.

Location

Room 101

Start Date

4-12-2018 3:00 PM

End Date

4-12-2018 4:15 PM

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Apr 12th, 3:00 PM Apr 12th, 4:15 PM

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

Room 101

Osteoarthritis is the most common joint disorder in the United States. It becomes most prevalent in adults reaching 60+ years of age and causes discomfort, decreased mobility and in some cases even excruciating pain. A large animal model for osteoarthritis is necessary for furthering the research and solution potential for this ubiquitous disease. Using an ovine model proves an effective technique in characterizing joint issues and with a demonstrated method of inducing the osteoarthritis over a period of months, not years, we can make hefty strides in furthering understanding of the disease. Our method involves two groups of surgically altered, mature ewes. One half undergoing ovariectomies and the other half a CCLD (Cranial Cruciate Ligament Desotomy). With one type of these surgeries and the use of oblique angle forced exercise over a period of approximately 4 months, significant effects of osteoarthritis will be observed. In the biological processes of osteoarthritis, the enzymes responsible for the degeneration of aggrecan, a key proteoglycan of cartilage, are upregulated in the animal. Inside the proteoglycan protein, the aggrecanases cause deterioration of the glycosaminoglycans. The regular maintainers of this enzyme’s activity are known as Tissue Inhibitor of Metalloproteinases (TIMPs). They keep the enzyme activity standard, however, a larger production of aggrecanases was noted in the osteoarthritis influenced cartilage. This study focuses on the up-regulating of full-length TIMP-3 protein signaling in situ using the introduction of a TIMP-3 transgene in a monolayer-cell/cartilage-tissue co-culture model. It is hypothesized that, in situ, up-regulation of cell-produced, full length TIMP-3 protein would decrease proteoglycan degradation. Understanding and utilizing these methods and research is hoped to make way for a new and better solution for the many affected by this disease.