LINC00473 exacerbates osteoarthritis development by promoting chondrocyte apoptosis and proinflammatory cytokine production through the miR‑424‑5p/LY6E axis

Abstract

Osteoarthritis (OA) is a common degenerative joint disease that has been identified as one of the major health burdens in aging individuals. Long non-coding RNAs (lncRNAs) participate in the development of diverse diseases, including OA. Among them, lncRNA long intergenic non-protein coding RNA 473 (LINC00473) is one of the few upregulated lncRNAs. The present study aimed to explore the role of LINC00473 and its regulatory mechanism in OA development. Flow cytometry analyses and ELISA were carried out to detect chondrocyte apoptosis and the concentration of proinflammatory cytokines, respectively. The results suggested that LINC00473 knockdown significantly reduced chondrocyte apoptosis and the production of proinflammatory cytokines in IL-1β-stimulated C28/I2 cells compared with transfection with small interfering RNA-negative control (si-NC). Western blot analyses were performed to examine protein levels of apoptotic markers (caspase-3, Bax and Bcl-2) in C28/I2 cells. Subsequently, an OA rat model was established to explore the role of LINC00473 in vivo. The results indicated that, compared with the OA + adeno-associated virus si-NC group, LINC00473 knockdown significantly suppressed the degradation of chondrocyte extracellular matrix and the production of proinflammatory cytokines in OA model rats. Furthermore, bioinformatics analysis, luciferase reporter and RNA immunoprecipitation assays indicated that LINC00473 served as a microRNA (miR)-424-5p sponge in C28/I2 cells, and that lymphocyte antigen 6 locus E (LY6E) was the downstream target. In addition, the inhibitory effects of LINC00473 knockdown on chondrocyte apoptosis and the inflammatory response could be reversed by LY6E overexpression in IL-1β-stimulated C28/I2 cells. In summary, the findings indicated that LINC00473 contributed to OA progression by modulating the miR-424-5p/LY6E axis, which may serve as a potential therapeutic strategy for patients with OA.

Blood RNA Sequencing Indicates Upregulated BATF2 and LY6E and Downregulated ISG15 and MT2A Expression in Children with Autism Spectrum Disorder

“…The consequences to the immune system of dysregulation of BATF2 , LY6E , ISG15 and MT2A in children with ASD ( Figure 1 ) are discussed in the above section. Notably, BATF2 was shown to promote inflammation in response to lipopolysaccharides or infection [ 49 ], and LY6E plays a role in T-cell activation and is upregulated by interferons [ 50 , 51 ]. Additionally, ISG15 is known to promote anti-inflammatory pathways [ 52 , 53 ].…”

Advances in Research on the Regulatory Roles of lncRNAs in Osteoarthritic Cartilage

“…Long intergenic noncoding RNAs (lincRNAs) have also been involved in the onset and development of OA. In particular, LINC00265, LINC00461, LINC00473, LINC01534, and LINC02288 [ 62 , 63 , 64 , 65 , 66 ] have been demonstrated to promote inflammatory responses by sponging related miRNAs. Among these lincRNAs, LINC00265, LINC00473, and LINC02288 have also been shown to promote apoptosis.…”

The emerging role of lncRNAs in osteoarthritis development and potential therapy

“…LINC00265 sponged miR-101–3p and regulated proliferation, inflammation and apoptosis of chondrocytes in osteoarthritis ( Zou et al, 2021 ). LINC00473 exacerbated progression of osteoarthritis by enhancement of proinflammatory cytokine production and induction of chondrocyte apoptosis via influencing the miR-424–5p/LY6E axis ( Fan et al, 2021 ). LINC01385 downregulation abolished progression of osteoarthritis via sponging miR-140–3p and increasing TLR4 expression ( Wang Z. et al, 2021 ).…”