Article
Serum microRNAs as novel osteoarthritis biomarkers
Search Medline for
Authors
Published: | November 6, 2018 |
---|
Outline
Text
Objectives: Osteoarthritis (OA) is a heterogeneous joint disease and a leading cause of pain and disability. Recently a link has been suggested between OA and metabolic syndrome introducing the new subtype of metabolic OA. Despite the significant socio-economic burden of OA, there is absence of effective non-arthroplasty treatment options. A major challenge for development of an effective OA therapy is disease detection at early stage. Therefore, identification of non-invasive and sensitive serum biomarkers will assist OA prognosis and early treatment. MicroRNAs (miRNAs) are novel small non-coding RNA molecules implicated in several diseases and in osteoarthritis (OA). Recent studies have reported that changes in levels of circulating miRNAs are associated with the disease pathophysiology, suggesting that miRNAs in circulation could be promising biomarkers. Even though miRNAs have been associated with OA pathogenesis, large scale analysis of microRNAs in the serum of OA patients has not been performed yet.
We aimed to identify a circulating miRNA signature for osteoarthritis (OA) patients and in combination with bioinformatics analysis to evaluate the utility of selected differentially expressed miRNAs in serum as potential OA biomarkers.
Methods: Serum samples collected from 12 primary OA patients and 12 healthy individuals were screened using the Agilent Human miRNA Microarray platform interrogating 2,549 miRNAs. Receiver Operating Characteristic (ROC) curves were constructed to evaluate the diagnostic performance of the deregulated miRNAs. Expression levels of selected miRNAs were validated by real-time PCR in all serum and in articular cartilage samples from OA patients (n=12) and healthy individuals (n=7). Bioinformatics analysis was used to investigate the involved pathways and target genes for the above miRNAs.
Results and conclusion: We identified 279 differentially expressed miRNAs in serum of OA patients. 205 miRNAs were up-regulated and 74 down-regulated. ROC analysis revealed 77 miRNAs with significant diagnostic value. Bioinformatics analysis in the 77 miRNAs revealed that their target-genes were involved in multiple signalling pathways associated with OA. Real-time-PCR validation in selected 7 out the /77 miRNAs revealed three significantly down-regulated miRNAs (hsa-miR-33b-3p, hsa-miR-671-3p and hsa-miR-140-3p) in the serum of OA patients, which were in silico predicted to be involved in metabolic processes. Hsa-miR-140-3p and hsa-miR-671-3p expression levels were consistently down-regulated in articular cartilage of OA patients compared to healthy individuals.
A serum miRNA signature was established, for the first time, using high density resolution miR-arrays in osteoarthritis patients. We identified a three-miRNA signature, hsa-miR-140-3p, hsa-miR-671-3p and hsa-miR-33b-3p in serum of OA patients, predicted to regulate metabolic processes, which could serve as a potential biomarker for the evaluation of OA risk and progression.