title: MiR-148a the epigenetic regulator of bone homeostasis is increased in plasma of osteoporotic postmenopausal women.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Biochemistry, Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, 1000, Ljubljana, Slovenia.
authors.forename: Ajda
authors.initials: A
authors.lastname: Bedene
authors.affiliation: Department of Clinical Biochemistry, Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, 1000, Ljubljana, Slovenia.
authors.forename: Simona
authors.initials: S
authors.lastname: Mencej Bedrač
authors.affiliation: Department of Clinical Biochemistry, Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, 1000, Ljubljana, Slovenia.
authors.forename: Lea
authors.initials: L
authors.lastname: Ješe
authors.affiliation: Department of Clinical Biochemistry, Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, 1000, Ljubljana, Slovenia.
authors.forename: Janja
authors.initials: J
authors.lastname: Marc
authors.affiliation: Department of Clinical Biochemistry, Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, 1000, Ljubljana, Slovenia.
authors.forename: Peter
authors.initials: P
authors.lastname: Vrtačnik
authors.affiliation: Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre, Ljubljana, Slovenia.
authors.forename: Janez
authors.initials: J
authors.lastname: Preželj
authors.affiliation: Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre, Ljubljana, Slovenia.
authors.forename: Tomaž
authors.initials: T
authors.lastname: Kocjan
authors.affiliation: Department of Clinical Biochemistry, Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, 1000, Ljubljana, Slovenia.
authors.forename: Tilen
authors.initials: T
authors.lastname: Kranjc
authors.affiliation: Department of Clinical Biochemistry, Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, 1000, Ljubljana, Slovenia. barbara.ostanek@ffa.uni-lj.si.
authors.forename: Barbara
authors.identifier: http://orcid.org/0000-0001-7158-8241
authors.initials: B
authors.lastname: Ostanek
mesh_terms: D000368:Aged; D015519:Bone Density / Q000235:genetics; D044127:Epigenesis, Genetic / Q000941:ethics / Q000235:genetics; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics*; D008875:Middle Aged; D010024:Osteoporosis / Q000097:blood* / Q000235:genetics*; D017698:Postmenopause / Q000097:blood* / Q000235:genetics*; D015995:Prevalence; D015203:Reproducibility of Results; D012307:Risk Factors; D012680:Sensitivity and Specificity; D017524:Slovenia
chemical_list: D005819:Genetic Markers; C550570:MIRN148 microRNA, human; D035683:MicroRNAs
keywords: Bone mineral density; Circulating microRNA; Fracture risk assessment tool; Postmenopausal osteoporosis; Trabecular bone score