Abstract
MicroRNAs and long non coding RNAs (lncRNA) shows an encouraging trend in the therapeutics of Osteoarthritis (OA), but there are limited studies showing the functional role of lncRNAs and miRs in OA pathogenesis. The study investigated the role of HOTAIR and its predicted target miR-17-3p in pathogenesis and identification of novel drug target of OA. LncRNAs were identified qualitatively and quantitatively by qRT-PCR, ELISA and Western blot analysis in C28/I2 cells. Results showed that LPS induced cell injury, cell apoptosis and influx of inflammatory cytokines (P<0.001) in C28/I2 cells. Over-expression of HOTAIR aggravated LPS-induced cell viability inhibition, cell apoptosis and inflammatory cytokines influx, while suppression of HOTAIR alleviated the injury (P<0.05). MiR-17-3p is a target of HOTAIR. Suppression of HOTAIR reduced LPS-induced- cell proliferation inhibition, cell apoptosis and inflammatory cytokines influx by overexpression of miR-17-3p, while suppression of miR-17-3p alleviated the injury in C28/I2 cells (P<0.05). Erythroblast transformation-specific translocation variant 1 (ETV1) is a target of miR-17-3p. Overexpression of ETV1 promoted LPS-induced-cell proliferation inhibition, cell apoptosis and inflammatory cytokines influx, while suppression of ETV1 alleviated the injury in C28/I2 cells (P<0.01). Signaling of LPS-induced cell injury was found to be via ETV1 by activation of MAPK/c-Jun and NF-κB pathways. In conclusion, LPS-induced cell injury was found to be mediated via suppression of miR-17-3p and promotion of ETV1 expression by activation of MAPK/c-Jun and NF-κB pathways. HOTAIR and miR-17-3p can be a potential therapeutic target in OA patients.