Project Grant R15AR080813

This three-year, $906,000 project grant from the National Institutes of Health's National Institute of Arthritis and Musculoskeletal and Skin Diseases will fund research into obesity-promoting protein malonylation and its role in chondrocyte metabolic dysfunction and osteoarthritis development. Specifically, the grantee - Ohio University - will investigate how obesity accelerates osteoarthritis through "carbon stress," which causes metabolic byproducts to accumulate in cartilage cells and decrease protein activity. They will test whether obesity promotes malonylation to accelerate osteoarthritis and determine how the SIRT5-malonylation pathway regulates cartilage degeneration under obesity-associated inflammatory conditions. Well-established mouse models and genetically modified mice will be used to examine the consequences of enhancing or inhibiting malonylation on osteoarthritis pathology. In vivo and in vitro metabolic profiling will assess effects on chondrocyte cellular metabolism. The research aims to provide a more comprehensive understanding of how obesity and aging damage joint cell metabolism and promote osteoarthritis, with the potential to identify new therapeutic targets.