Diurnal Changes in Serum Levels of Bone-Related Circulating MicroRNAs

Introduction Circulating microRNAs (miRNAs) may reflect the regulation of bone turnover at the tissue level. Bone resorption shows a clear diurnal rhythm, with lower levels of bone turnover in the afternoon. We aimed to study whether miRNAs that have been linked to bone metabolism might also show a diurnal rhythm.

Methods In a single-site observational longitudinal study, a panel of 19 bone-related miRNAs was measured using the osteomiR™ RT-qPCR assay in serum samples of 29 postmenopausal Caucasian women with and without osteoporosis between the age 50 and 70 years. Blood samples were taken on 7 occasions after overnight fasting: 08:30, 09:00, 09:30, 11:00, 12:00, 14:00, 15:00, with meals provided at 10:00 and 13:00. Quality of miRNA measurements was monitored with 3 spike-in and 2 hemolysis controls.

Results We analysed the data using mixed-effects model statistical approach and found statistically significant (P-value < 0.05) fixed effect between measured time-points of 9 miRNAs: hsa-miR-375, hsa-miR-214-3 p, hsa-miR-143-3 p, hsa-miR-335-5 p, hsa-miR-23a-3 p, hsa-miR-133b, hsa-miR-141-3 p, hsa-miR-127-3 p, hsa-miR-152-3 p. Additionally, we found a linear trend (P-value < 0.0001) in diurnal changes of 8 miRNAs: hsa-miR-375, hsa-miR-214-3 p, hsa-miR-143-3 p, hsa-miR-335-5 p, hsa-miR-23a-3 p, hsa-miR-133b, hsa-miR-127-3 p, hsa-miR-152-3 p.

Discussion Thus, miRNAs show a diurnal rhythm, and this may provide insight into the well-described changes in bone resorption through the day since some of these miRNAs have been shown to regulate bone resorption. For example, it has been reported that miR-214 promotes osteoclastogenesis by targeting Pten/PI3k/Akt pathway. At a practical level, it is appropriate to standardise the collection time and conditions to ensure reliable results.

Korrespondenzadresse Matthias Hackl, TAmiRNA GmbH, Leberstrasse 20, 1110 Vienna, Austria

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