MiR-148a the epigenetic regulator of bone homeostasis is increased in plasma of osteoporotic postmenopausal women

Wien Klin Wochenschr. 2016 Dec;128(Suppl 7):519-526. doi: 10.1007/s00508-016-1141-3. Epub 2016 Nov 29.

Abstract

Background: Osteoporosis is a prevalent skeletal disorder characterized by reduced bone mineral density and microarchitectural deterioration of bone tissue, resulting in bone fragility and low-trauma fractures. Imaging techniques are routinely used to detect low bone mass; however, they are unable to identify deterioration of bone quality. Recently, microRNAs have emerged as regulators of bone remodelling and potentially also as a new class of sensitive biomarkers of bone health to aid in diagnosis and treatment monitoring of osteoporosis.

Methods: To identify new plasma-based biomarkers associated with osteoporosis we analyzed microRNAs isolated from plasma samples of 74 postmenopausal women divided into osteoporotic (N = 17) and control groups (N = 57). A prior microRNA screening was performed where a few showed promise for further analysis. Quantitative polymerase chain reaction was used to investigate differences in expression of let-7d-5p, let-7e-5p, miR-30d-5p, miR-30e-5p, miR-126-3p, miR-148a-3p, miR-199a-3p, miR-423-5p and miR-574-5p between the two groups. Furthermore, correlation analysis between microRNA expression levels and patient bone mineral density measurements and fracture risk assessment tool (FRAX) as well as trabecular bone scores were performed.

Results: Expression of miR-148a-3p was significantly higher (p = 0.042) in the osteoporotic patient group compared to the controls. In addition, we identified correlations between miR-126-3p (ρ = 0.253, p = 0.032) and 423-5p (ρ = -0.230, p = 0.049) and parameters of bone quality and quantity.

Conclusion: The results from our study, together with the functional role of miR-148a-3p in bone suggest that this microRNA could be considered as a potential new plasma-based biomarker for pathological changes associated with osteoporosis.

Keywords: Bone mineral density; Circulating microRNA; Fracture risk assessment tool; Postmenopausal osteoporosis; Trabecular bone score.

MeSH terms

  • Aged
  • Bone Density / genetics
  • Epigenesis, Genetic / ethics
  • Epigenesis, Genetic / genetics
  • Female
  • Genetic Markers / genetics
  • Genetic Predisposition to Disease / epidemiology
  • Genetic Predisposition to Disease / genetics
  • Homeostasis / genetics
  • Humans
  • MicroRNAs / blood*
  • MicroRNAs / genetics*
  • Middle Aged
  • Osteoporosis / blood*
  • Osteoporosis / genetics*
  • Postmenopause / blood*
  • Postmenopause / genetics*
  • Prevalence
  • Reproducibility of Results
  • Risk Factors
  • Sensitivity and Specificity
  • Slovenia

Substances

  • Genetic Markers
  • MIRN148 microRNA, human
  • MicroRNAs