The Study of Muscle, Mobility and Aging with Knee OA

Project Summary Prevalence of osteoarthritis of the knee increases with age, and individuals with knee osteoarthritis have reduced muscle strength and changes in the composition of the muscle around the knee joint. The major mechanisms that drive age- and knee osteoarthritis-related loss of muscle mass and function are unclear - although inflammation, deficits in muscle quality, and impaired muscle regeneration, due to loss of stem cells (satellite cells) have all been implicated. Recently, we have determined that subjects in the SOMMA cohort with moderate to severe knee OA have some differences in their muscle composition compared to age similar controls. Specifically, knee OA subjects with and without pain have reduced muscle strength and increased intramuscular fat. Few studies have been performed that have evaluated the changes in the muscle composition at the tissue level in the muscles in elderly individuals with knee osteoarthritis compared to similar aged controls. To better understand skeletal muscle composition, we propose to add to the SOMMA database on muscle by performing additional stains to determine extracellular matrix abundance and organization and satellite cell abundance in muscle samples from patients with knee osteoarthritis and age-matched controls. It has been reported that knee osteoarthritis subjects have greater amounts of fibrosis, ECM and fat compared to subjects without knee osteoarthritis. This ancillary study proposal will expand on those observations by providing direct findings within the muscle of fibrosis and collagen. This information will also complement the deep cellular and molecular phenotyping already collected on the SOMMA cohort. This investigation has significant clinical relevance, as our earlier work in the SOMMA knee osteoarthritis study has uncovered phenotypic differences in participants with moderate to severe knee osteoarthritis compared to those without knee osteoarthritis. We are now proposing more cellular level insights and that may guide early preventative strategies to prevent strength loss in the muscle around a knee joint with osteoarthritis, and possibly develop targeted therapeutics for treating profound muscle weakness frequently observed in later stages of osteoarthritis. This work will be done by Christopher Fry, PhD at the University of Kentucky. He is the Associate Director of the Center for Muscle Biology, and his research group has contributed seminal manuscripts on muscle histology and function in osteoarthritis, aging and injury.