Grant Amount: $46,100

Dr. Alpana Ray, PhD, University of Missouri, Columbia

April 1, 2004 - March 31, 2006

Sponsor(s): American Bloodhound Club, Basenji Club of America, Inc. & Basenji Health Endowment, Golden Retriever Foundation, Newfoundland Club of America Charitable Trust, Norwegian Elkhound Association of America, Inc., Rottweiler Health Foundation, St. Bernard Club of America

Breed(s): -All Dogs

Disease(s): Hip Dysplasia

Abstract

Hip Dysplasia is a common disease of dogs that ultimately leads to osteoarthritis (OA), a serious debilitating condition, which at present, is treated by symptomatic management of pain. Accidental injuries also lead to the development of OA. Cartilage degeneration is fundamental to the pathogenesis of OA. We propose to study the transcriptional control of MMP-1, a major enzyme involved in the degradation of articular cartilage. Expression of MMP-1 gene and the corresponding protein is markedly increased under osteoarthritic condition. Because cytokines like IL-1 and TNF-a increase expression of MMP-1 and biomechanical factors also influence its expression in osteoarthritic, unstable joints, the objectives are to understand what components of the promoter region of canine MMP-1 gene are influenced by these factors. At present no data is available on canine MMP-1 gene regulation. This proposal is aimed towards understanding the regulation of canine MMP-1 gene expression in response to biomechanical stress and cytokines by isolating canine MMP-1 gene, identifying the regulatory elements in the promoter responsive to biomechanical stress and cytokines, and analyzing MMP-1 expression in chondrocytes of articular cartilage from normal and osteoarthritic dogs with the intent to develop novel therapeutic drugs to combat this disease.