Muscle morphological adaptations associated with tibiofemoral osteoarthritis

Knee osteoarthritis (OA) is associated with a clinically significant reduction of between 20-40% of quadriceps strength. In fact, quadriceps weakness is a central focus of the conservative management of OA. Intriguing evidence suggests that OA-associated quadriceps weakness may be the result of altered muscle quality, and that muscle weakness may actually precede the development of OA. Changes in the muscle environment, including inflammation, fibrosis, and fat infiltration, may contribute to muscle weakness associated with OA. Inflammatory cytokines such as IL-1â, IL-6 and TNFá have been shown to be elevated in the vastus lateralis of patients with OA who have muscle atrophy. In Aim 1, we will test the hypothesis that OA is associated with macrophage infiltration in muscle. Biopsies from the vastus lateralis of individuals with OA from the parent grant will be compared directly with age and activity matched healthy muscle biopsies collected at University of Kentucky. We propose to characterize the inflammatory state of muscle by determining macrophage abundance and polarization state (pro- or anti-inflammatory). Muscle fiber morphology, size and type, as well as muscle degeneration and fibrosis, will also be quantified on the same cryosections and the relationship to muscle strength determined. Whereas pro-inflammatory macrophages cause muscle damage, alternatively activated, anti-inflammatory macrophages in muscle have a reparative function. Alternatively activated macrophages may also be required for the hypertrophic response to exercise, by promoting muscle stem cell (satellite cell) survival, proliferation and differentiation. In Aim 2, we will test the hypothesis that OA is associated with alterations in muscle satellite cell activity such that they contribute to fat accumulation and fibrosis as opposed to muscle repair and maintenance. Satellite cell abundance, location and phenotype will be quantified in cryosections relative to macrophage profile, muscle fiber size and morphology, and the relationship to muscle strength determined. Defining the OA associated cellular and molecular adaptations in muscle may identify those most at risk for muscle weakness, identify individuals unlikely to respond to standard exercise regimens and form the basis of new and more effective rehabilitation programs.