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Title: Circulating microRNAs in osteoporosis
Author: Mandourah, A. Y.
ISNI:       0000 0004 6496 6189
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2017
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Osteoporosis is the most common age-related bone disease. It is clinically symptomless until the first fracture happens and once diagnosed it is often found to be associated with low bone mineral density (LBMD) of T-Score ≤ -2.5. Circulating microRNAs (miRNAs) have been used successfully as promising biomarkers to diagnose and assess the progression of complex diseases such as cancer and cardiovascular diseases, as well as the effectiveness of treatment. This research aims to identify circulatory miRNAs associated with the progression of osteoporosis in a test group of patients using advanced PCR arrays initially and the identified differentially-expressed miRNAs were validated in individual clinical specimens using RT-qPCR. The potential target genes were analyzed using bioinformatics tools. Ethical approval was obtained prior to patient recruitment. A total of 161 participants were recruited and assigned to five groups: Non-Osteoporosis control group (T-Score ≥-1), osteopenia (T-Score < -1 and > -2.5 SD), osteopenia with fracture (T-Score <-1 and >-2.5 SD), osteoporosis (T-Score ≤ -2.5 SD) and osteoporosis with fracture (T-Score ≤ -2.5 SD). RNAs were extracted and analyzed from all serum and plasma samples. A panel of 49 differentially expressed miRNAs (up or down by > 3 fold) between osteopenia and osteoporosis patient groups was identified using a miRNA PCR Array. Six miRNAs: miR-215-5p, miR-99a-5p, miR-100, miR-373-5p, miR-4516 and miR-122-5P, were significantly differentially-expressed between osteoporosis and osteopenia patients by initial RT-qPCR screening. Further analysis showed that the levels of circulating miRNAs: hsa-miR-373-5p, hsa-miR-122-5p and hsa-miR-215-5p and plasma hsa-4516 were associated with fragility fracture, and correlated with low bone mineral density. The results suggest that these miRNAs could be potential diagnostic biomarkers for osteoporosis in the future. Potential target genes of these miRNAs were also analyzed using bioinformatics tools. The project demonstrated that circulating miRNAs can be purified from serum and plasma and could be developed as critical diagnostic tools for osteoporosis.
Supervisor: Barraclough, D. ; Barraclough, R. ; Van 'T Hof, R. ; Ranganath, L. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral