Understanding the contribution of Lgr5+ interzone progenitor cells in articular cartilage development and regeneration

Abstract

Osteoarthritis (OA) is one of the major joint disease worldwide and the main feature of OA is the lost or damage of the articular cartilage (AC). AC known to have a poor healing ability but cells with progenitor markers expression were found in adult AC. However, the function and origin of these progenitors remain largely unknown. During the formation of the synovial joint, dedifferentiation of cells at the future joint site form a pool of progenitor cells namely the interzone. Leucine-rich repeat-containing, G-protein-coupled receptors (Lgr) 5 is a downstream target of Wnt signaling and a novel progenitor cell marker in hair follicles, intestinal crypt and various tissues. Data from our lab shows that Lgr5 is specifically expressed in the developing joint marking the interzone cell population, while lineage tracing of these Lgr5+ cells in the developing joint suggest that they differentiated into cells in AC, meniscus, ligaments and other joint compartments. Our hypothesis is that these Lgr5+ progenitors may have a potential to contribute the regeneration of AC. Genetic differences in wild type mice have a huge effects on healing ability in different strains of mice, MRL, good healer strain can fully heal an ear puncture and partially heal punctured AC while C57, bad healer strain cannot. By using these genetic differences in mouse and cross breed them with the mouse carrying a Lgr5 promoter controlled GFP reporter, it will give us a tool to understand these progenitor in growth and development and also their contribution during regeneration by inducing articular cartilage defects using a needle puncture model.