Long non-coding RNA LncHIFCAR promotes osteoarthritis development via positively regulating HIF-1α and activating the PI3K/AKT/mTOR pathway

Osteoarthritis (OA) is a progressive disease that characterized by synovial inflammation and loss of cartilage in the joint. This study aimed to elucidate the potential role of long non-coding RNA LncHIFCAR in the development of osteoarthritis (OA). Expression of LncHIFCAR and HIF-1α in OA and normal cartilage tissues were determined. ATDC5 chondrocyte cells were cultured under hypoxia condition to establish a cell model of OA. Additionally, LncHIFCAR was suppressed in ATDC5 cells and the effects of LncHIFCAR suppression on hypoxia-induced cell injury were investigated by assessing cell proliferation, apoptosis, inflammatory response, and matrix synthesis. Furthermore, interactions between LncHIFCAR and HIF-1α as well as HIF-1α target genes (VEGF and BNIP3) were explored. Additionally, whether LncHIFCAR affected the expression of PI3K/AKT/mTOR pathway-related proteins was detected. LncHIFCAR and HIF-1α were up-regulated in OA tissues. Hypoxia induced ATDC5 cell injury and increased LncHIFCAR expression. Suppression of LncHIFCAR significantly improved hypoxia-induced cell injury by promoting cell proliferation, inhibiting apoptosis, decreasing the secretion of TNF-α and IL-6, and suppressing the synthesis of MMPs. In addition, LncHIFCAR positively regulated HIF-1α and HIF-1α target genes (VEGF and BNIP3). LncHIFCAR promoted hypoxia-induced inflammatory response and matrix synthesis by upregulation of VEGF, and induced hypoxia-induced apoptosis via upregulation of BNIP3. Furthermore, LncHIFCAR significantly inhibited hypoxia-induced activation of PI3K/AKT/mTOR pathway. Our results indicate that LncHIFCAR is up-regulated in OA tissues and suppression of LncHIFCAR may improve hypoxia-induced cell injury via positively regulating HIF-1α and HIF-1α target genes (VEGF and BNIP3). The PI3K/AKT/mTOR pathway may thus be a possible mechanism to mediate LncHIFCAR function in OA development.