OA is a debilitating disease associated with pain and dysfunction caused by joint degeneration. There is currently no treatment regimen that is able to restore damaged cartilage to its normal phenotype or slow the progression of joint destruction. Confirming the contributions of the key molecular mediators in OA, as well as their interrelationships, will provide vital information and assist with defining appropriate pharmaceutical or molecular interventions. The central goal of this proposal is to generate a specific, localized reduction of interleukin-1 beta mediated signaling to define the role of such signaling in the progression of spontaneous osteoarthritis (OA) in the knee joints of Dunkin Hartley (DH) guinea pigs. Two methods will be examined to decrease IL-1 beta mediated signaling. First, RNA interference (RNAi) will be used to target and reduce the expression of three factors necessary for IL-1 beta mediated signaling: (1) IL-1beta; (2) type I IL-1 receptor; and (3) IL-1 beta converting enzyme. Second, a soluble competitive antagonist of IL-1 R1, interleukin-1 receptor antagonist, will be employed to reduce the effective concentration of soluble IL-1 beta. Both methods will utilize self-complementary adeno-associated viral serotype 5 vectors. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AR053805-03
Application #
7414706
Study Section
Special Emphasis Panel (ZRG1-F10-H (20))
Program Officer
Tyree, Bernadette
Project Start
2006-05-01
Project End
2009-04-30
Budget Start
2008-05-01
Budget End
2009-04-30
Support Year
3
Fiscal Year
2008
Total Cost
$52,048
Indirect Cost
Name
Ohio State University
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210