HOTAIR-induced apoptosis is mediated by sponging miR-130a-3p to repress chondrocyte autophagy in knee osteoarthritis.

Knee osteoarthritis (KOA) is a multifactorial disease characterized by the loss of articular cartilage. Hox transcript antisense intergenic RNA (HOTAIR) long non-coding RNA (lncRNA) is highly expressed in some cases of OA; however, its role in chondrocyte apoptosis in KOA and the mechanism by which HOTAIR mediates apoptosis in chondrocytes are not completely understood. Here, we evaluated the effects of HOTAIR on chondrocyte apoptosis in KOA. Our results showed that HOTAIR expression was significantly upregulated in cartilage tissues located at the femoral condyles or tibial plateaus of OA resection regions when compared with control regions in patients with normal non-weight-bearing area femoral condyle articular cartilage. Overexpression of HOTAIR caused a sharp increase in apoptosis rates and a reduction in the viability of chondrocytes. These effects were accompanied by the upregulation of Bax expression and the proteolytic cleavage of caspase 3 expression and downregulation of survivin and Bcl-2 expression. The silencing of HOTAIR produced the opposite effects. Moreover, the cartilaginous expression of miR-130a-3p was notably reduced in the OA resection regions of KOA patients. Luciferase assays showed that HOTAIR-adsorbed and reduced the levels of miR-130a-3p in chondrocytes. Further, inhibition of miR-130a-3p remarkably promoted the apoptosis of chondrocytes and repressed cell growth, while the silencing of HOTAIR could rescue the apoptosis mediated by miR-130a-3p inhibition. Chondrocyte autophagy was suppressed in a HOTAIR-dependent, miR-130a-3p inhibitor-mediated manner. Overall, our data revealed that aberrantly high expression of HOTAIR resulted in massive apoptosis events caused by the sponging of miR-130a-3p to suppress autophagy in chondrocytes, which, in turn, might trigger KOA. Therefore, inhibition of HOTAIR-mediated apoptosis might be a potential mechanism that can be targeted by gene therapy of KOA.