LOX-1 silencing activates the PI3K/AKT pathway to inhibit ox-LDL-induced apoptosis of THVECs

This study aimed to investigate the mechanism by which the LOX-1/PI3K/AKT signaling axis regulates oxidized low-density lipoprotein (ox-LDL)-induced apoptosis in type H bone vascular endothelial cells (THVECs).

Primary THVECs were isolated from rat trabecular bone and identified via coimmunofluorescence staining for CD31 and endomucin (EMCN). The cells were divided into four groups: control, ox-LDL (100 μg/mL), ox-LDL + LV (lentiviral LOX-1 knockdown), and ox-LDL + CON (LV-control). Additionally, an AKT inhibitor (MK-2206) was used to verify the role of PI3K/AKT signaling. Western blotting (WB) was used to measure the protein levels of LOX-1, PI3K, phosphorylated PI3K (p-PI3K), AKT, phosphorylated AKT (p-AKT), Bax,Cleaved-caspse 3,BMP2 and OPN. Flow cytometry was used to detect apoptosis rate and ROS (Reactive Oxygen Species) levels.

ox-LDL treatment significantly induced apoptosis in THVECs cells, upregulated the expression of LOX-1 and apoptoic proteins, promoted reactive oxygen species production, impaired bone remodeling, and reduced the phosphorylation levels of PI3K and AKT. Lentivirus-mediated LOX-1 knockdown reversed ox-LDL-induced endothelial dysfunction and promoted angiogenesis.

ox-LDL induces the silencing of the LOX-1 pathway, activates the PI3K/AKT pathway, promots apoptosis, and affects bone remodeling and angiogenesis. This suggests that targeting LOX-1 may become a potential strategy for the treatment of diabetic osteoporosis.