The Lnc-HOTAIR/miR122/PPAR γ signaling mediated the occurrence and continuous development of alcohol-induced Osteonecrosis of the femoral head

This study aimed to explore the mechanism of alcohol-induced Osteonecrosis of the femoral head (ONFH) through in vivo and in vitro experiments. In vitro, the Oil Red O staining showed that ethanol promoted extracellular adipogenesis in a dose-dependent manner. ALP staining and alizarin red staining showed that ethanol inhibited the formation of extracellular mineralization in a dose-dependent manner. The Oil Red O staining showed that miR122 mimics and Lnc-HOTAIR SiRNA rescued extracellular adipogenesis induced by ethanol in BMSCs. Besides, we found that the high expression of PPARγ in BMSCs recruited histone deacetylase 3 (HDAC3) and histone methyltransferase (SUV39H1), which reduced the histone acetylation level and increased the histone methylation level in the miR122 promoter region, respectively. In vivo, the levels of H3K9ac, H3K14ac, and H3K27ac of miR122 promoter region in the ethanol group were significantly decreased compared to the control group, respectively. The levels of H3K9me2 and H3K9me3 of miR122 promoter region in the ethanol group were significantly increased compared to the control group. Lnc-HOTAIR/miR-122/PPARγ signaling mediated the alcohol-induced ONFH in the rat model. Furthermore, the persistent decrease of miR122 expression mediated the continuous progress of alcohol-induced ONFH after stopping alcohol consumption.PMID:37024064 | DOI:10.1016/j.toxlet.2023.04.002

Source: Toxicology Letters - April 6, 2023 Category: Toxicology Authors: Hanwen Luo Guoping Le Mengting Lu Li Li Source Type: research