OBJECTIVE: Clinical and experimental studies demonstrate the important roles of vascular smooth muscle cells (VSMC) in the pathogenesis of @entity731 . We have previously determined that the osteogenic transcription factor @entity2447 is essential for VSMC @entity730 . The present study characterized @entity2447 -regulated signals and their potential roles in @entity729 . METHODS AND RESULTS: In vivo studies with atherogenic apolipoprotein E(-/-) @entity19 demonstrated that increased oxidative stress was associated with upregulation of @entity2447 ( @entity5271 ), which colocalized in the calcified @entity731 and were juxtaposed to infiltrated macrophages and osteoclast-like cells that are positively stained for an osteoclast marker, @entity5272 -resistant acid phosphatase. Mechanistic studies using RNA interference, a luciferase reporter system, chromatin immunoprecipitation, and electrophoretic mobility shift assays indicated that @entity2447 regulated the expression of @entity5271 via a direct binding to the 5'-flanking region of the @entity5271 . Functional characterization revealed that @entity5271 did not induce VSMC @entity730 , nor was @entity5271 required for oxidative stress-induced VSMC @entity730 . Using a coculture system, we demonstrated that VSMC-expressed @entity5271 induced migration as well as differentiation of bone marrow-derived macrophages into multinucleated, @entity5272 -resistant acid phosphatase-positive osteoclast-like cells. These effects were inhibited by the @entity5271 antagonist osteoprotegerin and with @entity121 in @entity2447 or @entity5271 . CONCLUSION: We demonstrate that @entity2447 directly binds to the promoter and controls the expression of @entity5271 , which mediates the crosstalk between calcifying VSMC and migration and differentiation of macrophages into osteoclast-like cells in the @entity731 . Our studies provide novel mechanistic insights into the regulation and function of VSMC-derived @entity5271 in the pathogenesis of @entity731 and @entity729 .

XXXX -upregulated receptor activator of nuclear factor kB ligand in calcifying smooth muscle cells promotes migration and osteoclastic differentiation of macrophages.

@entity5272 :: ('MESH:C029768', 'Chemical') :: ['tartrate'] @entity2447 :: ('12393(Tax:10090)', 'Gene') :: ['Runx2', 'Runx2 and receptor activator of nuclear factor kB ligand'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity5271 :: ('21943(Tax:10090)', 'Gene') :: ['RANKL'] @entity730 :: ('MESH:D002114', 'Disease') :: ['calcification'] @entity729 :: ('MESH:D061205', 'Disease') :: ['vascular calcification'] @entity731 :: ('MESH:D050197', 'Disease') :: ['atherosclerosis', 'atherosclerotic lesions'] @entity121 :: ('MESH:D009135', 'Disease') :: ['VSMC deficient']
@entity2447 :: (12393(Tax:10090),Gene) :: ['Runx2']
