Plasma microRNA signature associated with skeletal muscle wasting in post‐menopausal osteoporotic women

Author:

Faraldi Martina1ORCID,Sansoni Veronica1ORCID,Vitale Jacopo2,Perego Silvia1,Gomarasca Marta1ORCID,Verdelli Chiara3ORCID,Messina Carmelo45ORCID,Sconfienza Luca M.45ORCID,Banfi Giuseppe16ORCID,Corbetta Sabrina78ORCID,Lombardi Giovanni19ORCID

Affiliation:

1. Laboratory of Experimental Biochemistry and Molecular Biology IRCCS Istituto Ortopedico Galeazzi Milan Italy

2. Laboratory of Movement and Sport Science IRCCS Istituto Ortopedico Galeazzi Milan Italy

3. Laboratory of Experimental Endocrinology IRCCS Istituto Ortopedico Galeazzi Milan Italy

4. OU Diagnostic and Interventional Radiology IRCCS Istituto Ortopedico Galeazzi Milan Italy

5. Department of Biomedical Science for Health University of Milan Milan Italy

6. Vita‐Salute San Raffaele University Milan Italy

7. Department of Biomedical, Surgical and Dental Sciences University of Milan Milan Italy

8. Endocrinology and Diabetology Service IRCCS Istituto Ortopedico Galeazzi Milan Italy

9. Department of Athletics, Strength and Conditioning Poznań University of Physical Education Poznań Poland

Abstract

AbstractBackgroundSkeletal muscle mass wasting almost invariably accompanies bone loss in elderly, and the coexistence of these two conditions depends on the tight endocrine crosstalk existing between the two organs, other than the biomechanical coupling. Since the current diagnostics limitation in this field, and given the progressive population aging, more effective tools are needed. The aim of this study was to identify circulating microRNAs (miRNAs) as potential biomarkers for muscle mass wasting in post‐menopausal osteoporotic women.MethodsOne hundred seventy‐nine miRNAs were assayed by quantitative real‐time polymerase chain reaction in plasma samples from 28 otherwise healthy post‐menopausal osteoporotic women (73.4 ± 6.6 years old). The cohort was divided in tertiles based on appendicular skeletal muscle mass index (ASMMI) to better highlight the differences on skeletal muscle mass (first tertile: n = 9, ASMMI = 4.88 ± 0.40 kg·m−2; second tertile: n = 10, ASMMI = 5.73 ± 0.23 kg·m−2; third tertile: n = 9, ASMMI = 6.40 ± 0.22 kg·m−2). Receiver operating characteristic (ROC) curves were calculated to estimate the diagnostic potential of miRNAs. miRNAs displaying a statistically significant fold change ≥ ±1.5 and area under the curve (AUC) > 0.800 (P < 0.05) between the first and third tertiles were considered. A linear regression model was applied to estimate the association between miRNA expression and ASMMI in the whole population, adjusting for body mass index, age, total fat (measured by total‐body dual‐energy X‐ray absorptiometry [DXA]) and bone mineral density (measured by femur DXA). Circulating levels of adipo‐myokines were evaluated by bead‐based immunofluorescent assays and enzyme‐linked immunosorbent assays.ResultsFive miRNAs (hsa‐miR‐221‐3p, hsa‐miR‐374b‐5p, hsa‐miR‐146a‐5p, hsa‐miR‐126‐5p and hsa‐miR‐425‐5p) resulted down‐regulated and two miRNAs (hsa‐miR‐145‐5p and hsa‐miR‐25‐3p) were up‐regulated in the first tertile (relative‐low ASMMI) compared with the third tertile (relative‐high ASMMI) (fold change ≥ ±1.5; P‐value < 0.05). All the corresponding ROC curves had AUC > 0.8 (P < 0.05). Two signatures hsa‐miR‐126‐5p, hsa‐miR‐146a‐5p and hsa‐miR‐425‐5p; and hsa‐miR‐126‐5p, hsa‐miR‐146a‐5p, hsa‐miR‐145‐5p and hsa‐miR‐25‐3p showed the highest AUC, 0.914 (sensitivity = 77.78%; specificity = 100.00%) and 0.901 (sensitivity = 88.89%; specificity = 100.00%), respectively.ConclusionsIn this study, we identified, for the first time, two miRNA signatures, hsa‐miR‐126‐5p, hsa‐miR‐146a‐5p and hsa‐miR‐425‐5p; and hsa‐miR‐126‐5p, hsa‐miR‐146a‐5p, hsa‐miR‐145‐5p and hsa‐miR‐25‐3p, specifically associated with muscle mass wasting in post‐menopausal osteoporotic women.

Publisher

Wiley

Reference44 articles.

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