| First Author | Lin ME | Year | 2015 |
| Journal | Am J Pathol | Volume | 185 |
| Issue | 7 | Pages | 1958-69 |
| PubMed ID | 25987250 | Mgi Jnum | J:223299 |
| Mgi Id | MGI:5648648 | Doi | 10.1016/j.ajpath.2015.03.020 |
| Citation | Lin ME, et al. (2015) Runx2 Expression in Smooth Muscle Cells Is Required for Arterial Medial Calcification in Mice. Am J Pathol 185(7):1958-69 |
| abstractText | Arterial medial calcification (AMC) is a hallmark of aging, diabetes, and chronic kidney disease. Smooth muscle cell (SMC) transition to an osteogenic phenotype is a common feature of AMC, and is preceded by expression of runt-related transcription factor 2 (Runx2), a master regulator of bone development. Whether SMC-specific Runx2 expression is required for osteogenic phenotype change and AMC remains unknown. We therefore created an improved targeting construct to generate mice with floxed Runx2 alleles (Runx2(f/f)) that do not produce truncated Runx2 proteins after Cre recombination, thereby preventing potential off-target effects. SMC-specific deletion using SM22-recombinase transgenic allele mice (Runx2(DeltaSM)) led to viable mice with normal bone and arterial morphology. After vitamin D overload, arterial SMCs in Runx2(f/f) mice expressed Runx2, underwent osteogenic phenotype change, and developed severe AMC. In contrast, vitamin D-treated Runx2(DeltaSM) mice had no Runx2 in blood vessels, maintained SMC phenotype, and did not develop AMC. Runx2 deletion did not affect serum calcium, phosphate, fibroblast growth factor-23, or alkaline phosphatase levels. In vitro, Runx2(f/f) SMCs calcified to a much greater extent than those derived from Runx2(DeltaSM) mice. These data indicate a critical role of Runx2 in SMC osteogenic phenotype change and mineral deposition in a mouse model of AMC, suggesting that Runx2 and downstream osteogenic pathways in SMCs may be useful therapeutic targets for treating or preventing AMC in high-risk patients. |
