Abstract
Osteoporosis, related fracture/fragility, and osteoarthritis are age-related pathologies that, over recent years, have seen increasing incidence and prevalence due to population ageing. The diagnostic approaches to these pathologies suffer from limited sensitivity and specificity, also in monitoring the disease progression or treatment. For this reason, new biomarkers are desirable for improving the management of osteoporosis and osteoarthritis patients. The non-coding RNAs, called miRNAs, are key post-transcriptional factors in bone homeostasis, and promising circulating biomarkers for pathological conditions in which to perform a biopsy can be problematic. In fact, miRNAs can easily be detected in biological fluids (i.e., blood, serum, plasma) using methods with elevated sensitivity and specificity (RT-qPCR, microarray, and NGS). However, the analytical phases required for miRNAs’ evaluation still present some practical issues that limit their use in clinical practice. This review reveals miRNAs’ potential as circulating biomarkers for evaluating predisposition, diagnosis, and prognosis of osteoporosis (postmenopausal or idiopathic), bone fracture/fragility, and osteoarthritis, with a focus on pre-analytical, analytical, and post-analytical protocols used for their validation and thus on their clinical applicability. These evidences may support the definition of early diagnostic tools based on circulating miRNAs for bone diseases and osteoarthritis as well as for monitoring the effects of specific treatments.
Highlights
This review reveals miRNAs’ potential as circulating biomarkers for evaluating predisposition, diagnosis, and prognosis of osteoporosis, bone fracture/fragility, and osteoarthritis, with a focus on pre-analytical, analytical, and post-analytical protocols used for their validation and on their clinical applicability
Biomolecules 2020, 10, 589 obtained with minimal/non-invasive procedures [9,31]; (ii) their detection is based on polymerase chain reaction (PCR) methods, especially the real time quantitative PCR (RT-qPCR) that gives the most reproducible results with elevated specificity and sensitivity [32]; (iii) in human biofluids, they can be found both to bind to proteins or to be enclosed in exosomes, ectosomes or in high-density lipoproteins [33,34,35], showing an elevated stability
MiRNAs concentration, in plasma samples, measured by qPCR, revealed an elevated variability [9,36], that is physiological for healthy populations, and the levels of circulating miRNAs can be affected by any variables of blood processing [37,38,39]
Summary
A great effort has been made in searching novel circulating biomarkers that are able to identify pathological conditions and to support medical decisions. Pri-miRNA is processed in the nucleus by the DROSHA/DGCR8 complex to obtain the hairpin pre-miRNA, which undergoes to a cleavage in the cytoplasm by DICER that leads to the formation of a double stranded miRNA Both the strands can be incorporated into the RISC (RNA induced silencing complex) as mature miRNAs for targeting and binding the paired mRNA at the level of the “seed” miRNA region composed by the nucleotides in positions 2–7. Parallel to this canonical miRNA biogenesis, other pathways independent of DROSHA or DICER have been discovered [16,17]. The miRNAs validation process still presents various issues to be solved, but the use of circulating miRNAs as biomarkers for clinical practice will soon be applied and this is evident when miRNAs are used as diagnostic and/or prognostic biomarkers in tumors [30]
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