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Emerging evidence indicates that microRNAs (miRNAs) have important roles in regulating osteogenic differentiation and bone formation. Thus far, no study has established the pathophysiological role for miRNAs identified in human osteoporotic bone specimens. Here we found that elevated miR-214 levels correlated with a lower degree of bone formation in bone specimens from aged patients with fractures. We also found that osteoblast-specific manipulation of miR-214 levels by miR-214 antagomir treatment in miR-214 transgenic, ovariectomized, or hindlimb-unloaded mice revealed an inhibitory role of miR-214 in regulating bone formation. Further, in vitro osteoblast activity and matrix mineralization were promoted by antagomir-214 and decreased by agomir-214, and miR-214 directly targeted ATF4 to inhibit osteoblast activity. These data suggest that miR-214 has a crucial role in suppressing bone formation and that miR-214 inhibition in osteoblasts may be a potential anabolic strategy for ameliorating osteoporosis. [ABSTRACT FROM AUTHOR]

The purpose of this study was to find the circulating microRNAs (miRNAs) co-related with the severity of coronary artery calcification (CAC), and testify whether the selected miRNAs could reflect the obstructive coronary artery disease in symptomatic patients. Patients with chest pain and moderated risk for coronary artery disease (CAD) were characterized with coronary artery calcium score (CACS) from cardiac computed tomography (CT). We analyzed plasma miRNA levels of clinical matched 11 CAC (CACS > 100) and 6 non-CAC (CACS = 0) subjects by microarray profile. Microarray analysis identified 34 differentially expressed miRNAs between CAC and non CAC groups. Eight miRNAs (miR-223, miR-3135b, miR-133a-3p, miR-2861, miR-134, miR-191-3p, miR-3679-5p, miR-1229 in CAC patients) were significantly increased in CAC plasma in an independent clinical matched cohort. Four miRNAs (miR-2861, 134, 1229 and 3135b) were correlated with the degree of CAC. Validation test in angiographic cohort showed that miR-134, miR-3135b and miR-2861 were significantly changed in patients with obstructive CAD . We identified three significantly upregulated circulating miRNAs (miR-134, miR-3135b and 2861) correlated with CAC while detected obstructive coronary disease in symptomatic patients. [ABSTRACT FROM AUTHOR]