2. Understanding the consequences of synovial fibrosis
As we seek to better understand how pathologic changes to the synovial membrane affect its ability to maintain the health of the joint, a new area of interest in the lab focuses on elucidating the consequences of synovial fibrosis, a prominent feature of osteoarthritic joint pathology. It is known that the sensation of mechanical and physical forces is vital to cell function. In the highly mechanical microenvironment of musculoskeletal tissue a loss of naïve tissue architecture is a hallmark of disease. This introduces new mechanical and physical forces to all cells, both resident and infiltrating, during musculoskeletal tissue disease. During OA macrophages are key cellular mediators of synovial inflammation and influence pathologic cartilage and bone responses. Recent studies suggest that distinct macrophage clusters occupy specific niches within the synovium, deriving from both circulating monocyte and monocyte-independent lineages. Using methods of engineered mechanically tunable in-vitro systems and in-vivo models of OA disease progression, our goal is to understand how the dynamic physical environment changes in osteoarthritic synovium and differentially modulates resident and infiltrating macrophage function.