Dynamic Interplays of the Synovial Niche Ecosystem – DISNEy

The overarching goal of the DISNEy proposal (Dynamic Interplays of the Synovial Niche Ecosystem) is to gain new insights into the mechanisms involved in the homeostatic regulation of the synovial tissue niche by focusing on macrophages and their relationships with the microenvironment of the synovial niche including stromal cells such as fibroblasts and endothelial cells. I hypothesize that macrophage-stromal cells interplays are essential to the health span and longevity of the joint tissue. Specifically, I hypothesize that natural aging changes the synovial ecosystem including macrophage supply, fibroblast maintenance and joint vasculature anatomy, thereby altering homeostasis and function of the joints. The proposed research bridges an important intellectual gap between the osteo-articular research field and immunology by investigating the interface between stromal cells and innate immune cells under physiological conditions. The specific aims are to 1) determine how macrophages regulate the synovial niche microenvironment and 2) investigate how natural aging influences the interplays between macrophages and their stromal partners at both cellular and molecular levels.