Selected serum microRNA, abdominal aortic calcification and risk of osteoporotic fracture

Abstract

Context MicroRNA (miRNA) regulate post-transcriptionally the expression of osteogenesis and angiogenesis associated genes and emerge as potential non-invasive biomarkers in vascular and bone diseases. Severe abdominal aortic calcification (AAC) is associated with higher risk of cardiovascular event and of fragility fracture. Objective To identify miRNA linked to the aggravation of AAC and to incident osteoporotic fracture. Design Postmenopausal women (>50 years) with available serum at inclusion and data for each outcome (Kauppila score and incident fracture) were selected from the OFELY prospective cohort. We conducted a case-control study in 434 age-matched women, 50% with incident osteoporotic fracture over 20 years of follow-up and a second study in 183 women to explore AAC over 17 years. Methods Serum expression of three miRNA involved in vascular calcification and bone turnover regulation (miRs-26a-5p,-34a-5p, and -223-5p) was quantified at baseline by TaqMan Advanced miRNA technology and expressed by relative quantification. Outcomes were the association of miRNA levels with (1) incident osteoporotic fractures during 20 years, (2) AAC aggravation during 17 years. Results MiRNA level was not associated with incident fractures (miR-26a-5p: 1.06 vs 0.99, p = 0.07; miR-34a-5p: 1.15 vs 1.26, p = 0.35; miR-223a-5p: 1.01 vs 1.05, p = 0.32). 93 women had an increase in Kauppila score over 17 years while 90 did not. None of the miRNAs was associated with an aggravation in AAC (miR-26a-5p: 1.09 vs 1.10, p = 0.95; miR-34a-5p: 0.78 vs 0.73, p = 0.90; miR-223-5p: 0.97 vs 0.78, p = 0.11). Conclusions Circulating miR-26a-5p, -34a-5p and -223-5p are not significantly associated with incident fracture and AAC aggravation.

Circulating MicroRNAs as Novel Biomarkers for Osteoporosis and Fragility Fracture Risk: Is There a Use in Assessment Risk?

“…None of the three selected miRs (miR-26a-5p, miR-34a-5p, and miR-223-5p) by Pickering et al [67] showed significant differences in the serum of PM OP wF patients when compared to woF PM CTRs.…”

Circulating miRNAs: A New Opportunity in Bone Fragility

“…Pickering et al [ 64 ] examined the miRNA expression levels between 217 OP patients with fragility fractures and 217 HC without a history of fragility fractures, in addition to making an assessment of the same serum miRNAs in 183 women with abdominal aortic calcification (AAC). Three miRNAs (miR-26a-5p, miR-34-5p, and miR-223-5p) were selected from predictive programs (i.e., TargetScan, MiRWalk database), according to their relevance in vascular calcification and bone metabolism, and assayed by qPCR.…”

The Epigenetic Landscape of Vascular Calcification: An Integrative Perspective

“…On the other hand, Pickering et al reported that serum miR-26a, miR-34a, and miR-223 did not differ between those with and without VC progression [77], findings that are in contrast to those by Cavallari et al, who described that plasma miR-223 increased in those with ESRD under chronic dialysis [49]. It is likely that the numbers of subjects being tested, the timing of the assay for circulatory miRNAs, the controls used to derive miRNA data, and the biologic fluid assayed may account for the discrepancy we observed.…”

“…Interestingly, most reports (n = 40; 60.6%) looked into the pathogenic role of non-coding RNA in VC, while histone modification (n = 6; 9.1%) [53][54][55][56][57][58], DNA methylation (n = 8; 12.1%) [5,[59][60][61][62][63][64][65], and chromatin changes (n = 3; 4.5%) [66][67][68] accounted for one-fourth only. Nine (13.6%) [69][70][71][72][73][74][75][76][77] examined the discrepancy of epigenetic signatures between subjects or animals with and without VC but not their pathogenic influences. In the following sections, we summarize results from these reports and try to synthesize an inter-connected network of epigenetic regulation of VC based on the existing data assisted by bioinformatic integration.…”

“…There are nine studies examining solely the differences regarding individual epigenetic machinery between calcified and non-calcified specimens [69][70][71][72][73][74][75][76][77]. Differences in circulating miRNAs between plaques with and without calcification, and between patients with and without VC are the most frequently examined topics (seven reports), followed by differences in DNA methylation status of peripheral leukocytes (two reports).…”