Project: Understand how aging influences the synovial niche
Thanks to recent technological advances, there is a rich knowledge base about synovial cells’ roles in joint disorders including osteoarthritis and rheumatoid arthritis. Over the last 2 years we have come to understand that niche cells including macrophages and fibroblasts are highly dynamic and heterogeneous. Interestingly, the synovial tissue is divided into two well-defined sub-anatomical areas, the lining and sub-lining layers. The lining layer is formed by fibroblasts and macrophages that build an epithelial-like barrier flanking the intra-articular fluid, bone and cartilage. In contrast, the sublining layer consists of a loose connective tissue formed by fibroblasts, lymphatic vessels and small venules, and also contains macrophages. Matching this dual synovial architecture, recent reports enlightening synovial cells heterogeneity indicate that distinct subsets of macrophages (MHCII+ and CX3CR1+) and fibroblasts (Thy1+ and Thy1-) populate the two lining and sublining niches Although we are beginning to appreciate how inflammation influences the synovial tissue niche, far less is known about the stromal-immune cell interactions especially under physiological conditions. This is an important gap of knowledge because keeping healthy joints throughout life is essential as they represent central pivots connecting our body's parts together that enable us to perform, often unconsciously, remarkable daily life activities. According to WHO, it is estimated that by 2050 the number of people aged 65 would triple, thereby increasing to more than 1.5 billion people globally. While it seems common sense that aging alters joint physiology, we hardly understand the underlying biology. Understanding the physiological synovial network at the cellular and molecular levels and how aging alters the synovial niche-at-large are the next critical steps that motivate this proposal.