Untargeted Metabolomic Analysis of AMPKalpha1 knockout mouse knees reveals sexual dimorphism in osteoarthritis progression

Soumilee Chaudhuri,Dr.Ru Liu-Bryan* and Dr. Ronald K. June,Department of Mechanical & Industrial Engineering, Montana State University Bozeman, 220 Roberts Hall, Bozeman MT- 59715 *Dr. Ru Liu-Bryan, Divison of Rhuematology,Allergy, and Immunology ,UC San Diego School of Medicine, 9500 Gilman Drive, mail code 9111K, San Diego, CA 92093

Osteoarthritis (OA) is a chronic degenerative disease of articular cartilage and other joint tissues. It is highly prevalent, affecting more than 27 million individuals in the United States. Being a chronic ailment, there is currently no cure for osteoarthritis, although treatments are available for partial management of symptoms and for relief. Sex-specific and metabolic associations in the origin and severity of osteoarthritis have been matters of extensive research, and OA is more prevalent in women than men. The goal of this project is to explore metabolism in osteoarthritis by studying the sex-specific differences in metabolomic profiles of Wildtype (WT) and AMPKalpha1 mutant (KO) mice, as AMPKalpha1 is a master regulator of metabolism. Metabolomic profiling detects metabolites derived from biological processes, and the analysis of the metabolites from these samples provides critical information about metabolic pathways that are perturbed during OA development. The results of untargeted metabolomic study of whole joint tissues of Wild-Type (WT) and AMPKalphal knockout (KO) mice established a connection between energy metabolism pathways and joint aging. Global metabolomic profiles were generated based on 2157 metabolite features detected in the whole-joint extracts of wild-type and alpha-Ampk KO mice.Metabolism of essential amino acids (arginine, proline,etc) was higher in female KO mice;female mutant mice also showed a cluster of low intensity metabolites.These data provided insight into AMPK function in aging joints and revealed elevated metabolic pathways in female mutant mice; this implied sex-specific differences in the prognosis of OA, and an intricate connection amongst AMPK mutation, sex, and osteoarthritis development. A comprehensive understanding of OA pathogenesis in female AMPK mutant mice, would be instrumental in developing targeted novel therapies for prevention of osteoarthritis. The long term goal is to identify disease biomarkers and engineer appropriate therapeutic interventions to slow the development of osteoarthritis. 

Additional Abstract Information

Presenter: Soumilee Chaudhuri

Institution: Montana State University Bozeman

Type: Poster

Subject: Biological & Chemical Engineering

Status: Approved

Time and Location

Session: Poster 2
Date/Time: Mon 3:00pm-4:00pm
Session Number: 2532