| First Author | Wang W | Year | 2014 |
| Journal | Stem Cells Dev | Volume | 23 |
| Issue | 12 | Pages | 1392-404 |
| PubMed ID | 24512598 | Mgi Jnum | J:329745 |
| Mgi Id | MGI:6840520 | Doi | 10.1089/scd.2013.0528 |
| Citation | Wang W, et al. (2014) Mesenchymal stem cells recruited by active TGFbeta contribute to osteogenic vascular calcification. Stem Cells Dev 23(12):1392-404 |
| abstractText | 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 (TGFbeta) 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 TGFbeta 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 with shared blood circulation by crossing ldlr(-/-)mice fed HFD with transgenic mice, in which all the MSC-derived cells were fluorescently labeled. The labeled cells were detected not only in the peripheral blood but also in the arterial lesions in ldlr(-/-) mouse partners, and these blood circulation-originated cells gave rise to Ocn(+) osteoblastic cells at the arterial lesions. Both active TGFbeta1 levels and MSCs in circulating blood were upregulated at the same time points when these cells appeared at the aortic tissue. Further, conditioned medium prepared by incubating the aortae from ldlr(-/-)mice fed HFD stimulated the migration of MSCs in the ex vivo transwell assays, and either TGFbeta neutralizing antibody or the inhibitor of TGFbeta Receptor I kinase (TbetaRI) antagonized this effect. Importantly, treatment of the mice with TbetaRI inhibitor blocked elevated blood MSC numbers and their recruitment to the arterial lesions. These findings suggest that TGFbeta-recruited MSCs to the diseased vasculature contribute to the development of osteogenic vascular calcification. |
