Circulating MiR-21 expression is upregulated after 30 days of head-down tilt bed rest

Relative expression of miR-21-5p in serum was upregulated in response to 30 days of bed rest, and miRNA fold changes were positively associated with serum calcium changes.

Circulating miRNAs (c-miRNAs) have potential as biomarkers of cellular activity, and they may play a role in cell-to-cell communication. The purpose of this study was to examine c-miRNA and bone marker responses to a 30-day six-degree head-down bed rest protocol at an ambient 0.5% CO₂.

Eleven participants (6 males/5 females, 25-50 years) had fasting blood draws taken 3 days before and immediately after completing the 30-day bed rest protocol at the Institute for Aerospace Medicine in Germany. Serum relative expression of miRNAs associated with bone function (miR-21-5p, -100-5p, -125b-5p, -126-3p) were analyzed using qPCR, and serum bone markers were quantitated using ELISA.

Serum bone markers, sclerostin, and calcium significantly increased (p ≤ 0.036), and total hip aBMD significantly decreased (p = 0.003) post bed rest. Serum miR-21-5p relative expression was significantly upregulated (p = 0.018) post bed rest. Fold changes in miR-126-3p (r = 0.82, p = 0.002) and miR-21-5p (r = 0.62, p = 0.042) were positively correlated with absolute change in serum calcium. There were no sex differences in miRNA responses; women had greater percent increases in TRAP5b (37.3% vs. 16.9% p = 0.021) and greater percent decreases in total hip aBMD (- 2.15% vs. - 0.69%, p = 0.034) than men.

c-miR-21-5p has potential as a biomarker of bone resorption and bone loss in an unloading condition. The upregulation of miR-21-5p may reflect an increase in osteoclast activity after bed rest, which is corroborated by the increase in TRAP5b.