Abstract
Osteoarthritis (OA) is a chronic and prevalent degenerative musculoskeletal disorder, which is characterized by articular cartilage degradation and joint inflammation. MicroRNA-203a (miR-203a) has been shown to be involved in multiple pathological processes during OA, but little is known about its function in chondrocyte extracellular matrix (ECM) degradation. In the present study, we aimed to elucidate the effects of miR-203a on articular cartilage degradation and joint inflammation. We observed that the miR-203a level was significantly up-regulated in OA tissues and in an in vitro model of OA, respectively. Inhibition of miR-203a significantly alleviated the interleukin (IL)-1β-induced inflammatory response and ECM degradation in chondrocytes. Moreover, mothers against decapentaplegic homolog 3 (Smad3), a key factor in maintaining chondrocyte homeostasis, was identified as a putative target of miR-203a in chondrocytes. More importantly, inhibition of Smad3 impaired the inhibitory effects of the miR-203a on IL-1β-induced inflammatory response and ECM degradation. Collectively, these results demonstrated that miR-203a may contribute to articular cartilage degradation of OA by targeting Smad3, suggesting a novel therapeutic target for the treatment of OA.
Highlights
Osteoarthritis (OA) is the most common chronic joint disease, which is characterized by articular cartilage degradation, joint inflammation and secondary bone hyperplasia [1]
The results demonstrated that IL-1β stimulation significantly inhibited cell viability and increased apoptosis, whereas knockdown of miR-203a reversed these effects of IL-1β in chondrocytes (Figure 2B–D; P
We revealed that miR-203a was up-regulated in OA articular cartilage tissues and IL-1β-induced chondrocytes
Summary
Osteoarthritis (OA) is the most common chronic joint disease, which is characterized by articular cartilage degradation, joint inflammation and secondary bone hyperplasia [1]. Chondrocytes are the only cell type present in articular cartilage and play a key role in tissue homeostasis and maintaining matrix integrity [2]. MicroRNAs (miRNAs) are endogenous small noncoding RNAs of 18–24 nucleotides in length, which act as a unique regulator of gene expression at the post-transcriptional level by inhibiting translation or promoting RNA degradation [4]. More and more miRNAs are found to be abnormally expressed in human OA cartilage tissue, among which some have been shown to play a role in the pathological processes of OA [5,6]. Several miRNAs have been reported to regulate inflammation and articular cartilage degradation in OA, such as miR-138 and miR-101.
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