Up-regulation of plasma miRNA-21 and miRNA-422a in postmenopausal osteoporosis

PLoS One. 2023 Oct 18;18(10):e0287458. doi: 10.1371/journal.pone.0287458. eCollection 2023.

Abstract

Background: Many researchers focused on diverse miRNAs in the progression of osteoporosis in postmenopausal women. This study aimed to evaluate the association between plasma miRNA-21-5p and miRNA-422a with osteoporosis in postmenopausal women.

Methods: This cross-sectional comparative study was performed on 126 randomly selected postmenopausal women aged 50-65, including 65 osteoporotic and 61 normal-bone mineral density (BMD) women. miRNA-21 and miRNA-422a were identified using qRT-PCR in these women. BMD was evaluated by the dual-energy X-ray absorptiometry method. A binary logistic regression model adjusted for confounders was used to evaluate the associations between plasma miRNAs' expression levels and osteoporosis. The Area Under Curve (AUC) was calculated to differentiate low BMD in the postmenopausal period using Receiver-Operator Characteristic (ROC) curves.

Results: miRNA-21 and miRNA-422a were significantly up-regulated in osteoporotic compared to non-osteoporotic postmenopausal women. The expression levels of miRNA-21 and miRNA-422a indicated a significant reverse correlation with both lumbar spine and femoral neck density. After adjusting the confounders, the likelihood of osteoporosis in the postmenopausal women with under the median plasma levels of miRNA-21 (OR = 0.025; 95% CI: 0.003 to 0.198, p<0.001) and miRNA-422a (OR = 0.037; 95% CI: 0.007 to 0.211, p<0.001) was significantly less than the women with the levels above the median. There were significant inverse correlations between miRNA-21 (p<0.001, r = -0.511) and miRNA-422a (p<0.001, r = -0.682) with BMD-lumbar spine as well as an inverse correlation between miRNA-21(p<0.001, r = -0.374) and miRNA-422a (p<0.001, r = -0.602) with BMD-femoral neck. The AUC (95%CI) for miRNA-21 and miRNA-422a was 0.84 (0.77 to 0.91) and 0.98 (0.96 to 0.99), respectively. ROC analysis illustrated that sensitivity and specificity values were 83.1% and 74%, respectively, for miRNA-21 at the cut-off point of 3.38. Also, at the cut-off point of 2.86, a sensitivity of 94% as well as a specificity of 89% was determined for miRNA-422a.

Conclusions: This study indicated that the odds of osteoporosis in postmenopausal women increased with the higher expression of plasma miRNA-21 and miRNA-422a.

MeSH terms

  • Absorptiometry, Photon / methods
  • Bone Density / genetics
  • Cross-Sectional Studies
  • Female
  • Humans
  • Lumbar Vertebrae
  • MicroRNAs* / genetics
  • Osteoporosis* / complications
  • Osteoporosis, Postmenopausal*
  • Up-Regulation

Substances

  • MicroRNAs
  • MIRN21 microRNA, human
  • MIRN422 microRNA, human

Grants and funding

The Vice-chancellor for Research and Technology, Tabriz University of Medical Sciences financially funded the original research (grant no: 61494). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No any authors received a salary from funder.