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| Status |
Public on Oct 17, 2017 |
| Title |
Circulating microRNA signature as novel biomarkers for osteoarthritis development |
| Organism |
Homo sapiens |
| Experiment type |
Non-coding RNA profiling by array
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| Summary |
Introduction: MicroRNAs (miRNAs) in circulation have emerged as promising biomarkers. In this study we aimed to identify a circulating miRNA signature for osteoarthritis (OA) patients. Methods: Serum samples were collected from 12 primary OA patients and 12 healthy individuals and were screened using the Agilent Human miRNA Microarray. Receiver Operating Characteristic (ROC) curves were constructed to evaluate the diagnostic performance of the deregulated miRNAs. Expression levels of selected miRNAs were validated by quantitative Real-time PCR (qRT-PCR) in all serum samples 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 of the above miRNAs. Results: We identified 279 differentially expressed miRNAs in the serum of OA patients compared to healthy controls. 205 (73.5%) were up-regulated and 74 (26.5%) down-regulated. ROC analysis revealed that 77 miRNAs had area under the curve (AUC)> 0.8 and p<0.05. Bioinformatics analysis in 7 out of the 77 selected miRNAs (hsa-miR-33b-3p, hsa-miR-4284, hsa-miR-671-3p, hsa-miR-663a, hsa-miR-140-3p, hsa-miR-150-5p and hsa-miR-1233-3p) revealed that their target genes were involved in multiple signaling pathways, among which FOXO, mTOR, pI3K/akt, lipid metabolism and TGF-β. A serum miRNA signature including three down-regulated miRNAs (hsa-miR-33b-3p, hsa-miR-671-3p and hsa-miR-140-3p) were also verified by qRT-PCR in OA patients. Furthermore, we found that hsa-miR-140-3p, hsa-miR-671-3p and potentially hsa-miR-33b-3p expression levels were consistently down-regulated in articular cartilage of OA patients compared to healthy individuals. Conclusions: A global miRNA serum signature was revealed in OA patients. We identified a three- miRNA signature in peripheral serum which could be potential osteoarthritis biomarkers.
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| Overall design |
Serum samples were collected from 12 patients with primary OA (9 females, 3 males, ages: 69.83 ± 4.83 years) undergoing total knee replacement surgery at the Orthopaedics Department of the University Hospital of Larissa. Radiographs were obtained before surgery and graded using the Kellgren-Lawrence system according to the following criteria: grade 1 (doubtful narrowing of joint space and possible osteophytes), grade 2 (definite osteophytes and possible narrowing of joint space), grade 3 (moderate multiple osteophytes, definite narrowing of joint space and some sclerosis and possible deformity of bone ends) and grade 4 (large osteophytes, marked narrowing of joint space, severe sclerosis and definite deformity of bone ends). All OA patients had a Kellgren-Lawrence grade ≥3. The assessment of the radiographs by two independent expert observers was blinded. Patients with rheumatoid arthritis and other autoimmune disease as well as chondrodysplasias, infection-induced OA and post-traumatic OA were excluded from the study. As controls, serum samples were obtained from 12 healthy individuals (6 females, 6 males, ages: 64,25± 5,04 years) undergoing knee fracture repair surgery, with no history of joint disease, who did not show clinical manifestations compatible with OA when specifically explored by radiography. Consent was obtained from each participant. The study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the local ethical committee of the University Hospital of Larissa. Articular cartilage samples (n=12) were collected from femoral condyles and tibial plateaus of the same OA patients, while normal articular cartilage was obtained from 7 out of the 12 healthy individuals.
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| Contributor(s) |
Ntoumou E, Braoudaki M, Lambrou GI, Tzetis M, Tsezou A |
| Citation(s) |
29255496 |
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| Submission date |
Oct 16, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
George I Lambrou |
| E-mail(s) |
glamprou@med.uoa.gr
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| Phone |
00302107467427
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| Organization name |
National and Kapodistrian University of Athens
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| Department |
First Department of Pediatrics
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| Lab |
Choremeio Research Laboratory
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| Street address |
Thivon & Levadeias
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| City |
Athens |
| State/province |
Attiki |
| ZIP/Postal code |
11527 |
| Country |
Greece |
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| Platforms (1) |
| GPL21575 |
Agilent-070156 Human_miRNA_V21.0_Microarray 046064 (Feature Number version) |
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| Samples (24)
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| Relations |
| BioProject |
PRJNA414440 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE105027_RAW.tar |
66.1 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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