Suppression of lncRNA-MALAT1 activity ameliorates femoral head necrosis by modulating mTOR signaling.

Abstract

Avascular necrosis of the femoral head (ANFH) is one of the most complicated bone disorders; management remains challenging. We evaluated the effect of lncRNA-MALAT1 suppression on ANFH rats. Dexamethasone was injected intravenously at 0.5 mg/kg daily for 30 days to induce ANFH; an lncRNA-MALAT1 inhibitor group received the inhibitor for the entire 30 days. LncRNA-MALAT1 suppression was evaluated by measuring blood hexosamine and hydroxyproline levels, and that of circulating endothelial progenitor cells (EPCs). Changes in femoral head bone ultrastructure were assessed via transmission electron microscopy and magnetic resonance imaging (MRI). We used reverse transcription polymerase chain reaction (RT-PCR) and Western blotting to measure gene and protein expression levels in femoral head tissue. The blood hexosamine level rose and that of hydroxyproline fell in the LncRNA-MALAT1 inhibitor group compared to the ANFH group. LncRNA-MALAT1 suppression increased the level of circulating EPCs. Ultrastructural changes in the femoral bone head were alleviated by the lncRNA-MALAT1 inhibitor. LncRNA-MALAT1 suppression lowered the levels of AMPK, mTOR, and Beclin-1 in rat tissue homogenates. LncRNA-MALAT1 suppression attenuated dexamethasone-induced femoral head necrosis by regulating AMPK/mTOR/Beclin-1 signaling.