Abstract
Osteoarthritis (OA) is a common degenerative joint disorder, which involves articular cartilage degeneration as well as joint inflammatory reactions. The recent studies have identified microRNA (miRNA) as one of the epigenetic mechanisms for the regulation of gene expression. Here we aim to reveal the role of miRNA in the regulation of gene expression in articular chondrocytes and its significance in the OA pathogenesis. In the present study, miRNA profiling was performed using OA cartilage and normal healthy cartilage tissues. As compared to their levels in normal cells and tissues, miR-27a expression was found to be upregulated in OA cartilage and IL-1β-treated articular chondrocytes. TUNEL staining, as well as flow cytometry with Annexin V-FITC/PI double labeling indicated that miR-27a inhibition reduced the apoptosis of IL-1β-treated articular chondrocytes. Bioinformatics prediction and the dual-luciferase reporter assay indicated that miR-27a targeted the 3′-UTR of the PI3K gene to silence it. The PI3K mRNA level in OA cartilage and IL-1β-treated articular chondrocytes was also downregulated, comparing with normal cells and tissues. Transfection of chondrocytes transfected with the miR-27a inhibitor upregulated the PI3K expression. This study demonstrated miR-27a is a regulator of the PI3K-Akt-mTOR axis in human chondrocytes and could participate in OA pathogenesis.
Highlights
Osteoarthritis (OA), a frequently seen degenerative joint disorder, is associated with pain, as well as joint malfunction [1]
MiR-27a is upregulated in OA cartilage, as well as IL-1β-supplemented articular chondrocytes
We found that the miR-27a expression was remarkably increased in OA cartilage samples, compared to healthy controls (Figure 1A, 1B)
Summary
Osteoarthritis (OA), a frequently seen degenerative joint disorder, is associated with pain, as well as joint malfunction [1]. OA displays the consistent degeneration of articular cartilage, causing the imbalanced generation and degeneration of articular chondrocyte ECM (extracellular matrix) [2]. Human and animal researches have widely reported abnormal gene expression in OA articular chondrocytes led to its pathogenesis [6], the regulatory mechanism for the expression of these genes in articular chondrocytes remains to be elucidated. MicroRNAs (miRNAs) that possess epigenetic-like properties in the regulation of gene expression have been considered as one of the epigenetic mechanisms [7]. Innovative targets of OA, such as genes participating in OA generation, have been revealed with the help of genetic networks, and epigenetic, as well as miRNA-based methods [1]
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