Mesenchymal stem cells recruited by active TGFβ contribute to osteogenic vascular calcification.

Vascular calcification is an actively regulated process that culminates in organized extracellular matrix mineral deposition by osteoblast-like cells. The origins of the osteoblastic cells involved in this process and the underlying mechanisms remain to be defined. We previously revealed that active transforming growth factor (TGFβ) released from the injured arteries mobilizes mesenchymal stem cells (MSCs) to the blood stream and recruits the cells to the injured vessels for neointima formation. In this study, we used a low-density lipoprotein receptor (LDLR)-deficient mouse model (ldlr−/−), which develop progressive arterial calcification after having fed high-fat western diets (HFD), to examine whether TGFβ is involved in the mobilization of MSCs during vascular calcification. Nestin+/Sca1+ cells were recruited to the diseased aorta at earlier time points, and osteocalcin+ osteoblasts and the aortic calcification were seen at later time point in these mice. Importantly, we generated parabiotic pairs wit...