Abstract: Objective To investigate the effect and potential mechanism of long non-codingRNA HAGLR on the inflammatory response and apoptosis of chondrocytes in rats with osteoarthritis. Methods  StarBase and luciferase gene reporter assay were used to predict and verify the interaction between lncHAGLR and miR-26a. To investigate the regulatory role of lncHAGLR on miR-26a expression, C518 cells were divided into 4 groups: si-lncHAGLR group, si-NC group, miR-26ainhibitor group, and inhibitor-NC group. Furthermore, to study whether lncHAGLR regulates in flammation and apoptosis in C518 cells by modulating miR-26a, C518 cells were divided into 5 groups: Control group, IL-1β group, IL-1β + si-NC group, IL-1β + si-lncHAGLR group, and IL-1β + si-lncHAGLR + miR-26a-inhibitor group. Real-time quantitative PCR ( qRT-PCR) was used to analyze the expression levels of lncHAGLR and miR-26a. The proliferation, cytotoxicity and apoptosis of C518 cells were detected by MTT, lactate dehydrogenase (LDH) Kit and flow cytometry (FCM). Western blotting assay was used to detect the protein expression levels of cleavedCASPASE3, NF-κB P65, and phosphorylated NF-κB P65 (P-NF-κB P65). The levels of releasedinflammatory factors (TNF-α and IL-6) were detected by ELISA. Results lncHAGLR directly targeted miR-26a. The expression level of lncHAGLR in the IL-1β group was significantly higher than that in the Control group, and the expression level of miR-26a was significantly lower than that inthe Control group (all P< 0. 05). In addition, cells in the IL-1β + si-lncHAGLR group had reducedIL-1β-induced chondrocyte inflammation, inhibited apoptosis, increased cell viabilities, decreased release of LDH, inhibited expression of cleaved-CASPASE3, and decreased secretions of TNF-αand IL-6 ( all P < 0. 05). Moreover, the expression level of P-NF-κB P65 was decreased (P<0. 05). Adding of miR-26a-inhibitor ( IL-1β + si-lncHAGLR + miR-26a-inhibitor group) reversedthe performances of cells in the IL-1β + si-lncHAGLR group (all P < 0. 05). Conclusion lncHAGLR promotes the inflammatory response and apoptosis of chondrocytes in osteoarthritis rats by inhibiting the activation of NF-κB through targeting miR-26a, suggesting that lncHAGLR may be avaluable therapeutic target for osteoarthritis treatment.

Key words: lncHAGLR, osteoarthritis, C518 cells, cell apoptosis, miR-26a, NF-κB P65