Rôle de LRP1 et PPARgamma dans la calcification vasculaire et du cartilage – LRP/PPARchondro

Calcification of the extracellular matrix (ECM) can be physiological or pathological. Physiological calcification occurs in bone during skeletogenesis whereas pathological calcification can occur in arteries, cartilage and other soft tissues. During arterial calcification cells lose their expression of vascular smooth muscle cell markers and begun to express more chondrogenic markers such as the master regulator of chondrogenesis Sox9. However, the mechanisms that regulate vascular calcification, the origins of the vascular progenitors, the paracrine regulation, and the signaling pathways involved are poorly understood. Recently, we obtained preliminary results that identified the Low Density Lipoprotein Receptor-related Protein 1 (LRP1) and the nuclear receptor PPARgamma as playing a critical role in chondrocyte differentiation in the vascular wall. The main goal of this project is to determine, using molecular and cellular approaches, and by developing tissue specific loss of function mouse models, the molecular mechanisms by which LRP1 and PPARgamma control chondrogenesis. Through this line of research, we hope to develop new tools to prevent vascular calcification during atherosclerosis, and provide insights into the process of chondrogenesis and cartilage repair.