Vascular endothelial growth factor gene silencing suppresses wear debris-induced inflammation

Abstract

Aseptic loosening is the most common complication of total joint replacement, which most likely results from an inflammatory response to wear debris shed from the implant. In this study we aimed to investigate whether the lentivirus-mediated microRNA (miRNA) targeting vascular endothelial growth factor (VEGF) could inhibit wear debris-induced inflammation in a murine model. Titanium alloy particles were introduced into established air pouches on BALB/c mice, followed by implantation of calvarial bone from a syngeneic mouse. After treatment by locally delivered lentivirus-mediated VEGF miRNA, inflammatory tissues were collected for histology and molecular analysis. We found that (1) locally delivered miRNA inhibited titanium alloy particle-induced tissue inflammation, including the diminished pouch membrane thickness and reduced inflammatory cellular infiltration and that (2) locally delivered miRNA inhibited expressions of the inflammatory cytokines VEGF, tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and receptor activator of nuclear factor kappa B ligand (RANKL). These findings suggest that local VEGF inhibition might be a promising therapeutic candidate to alleviate particle-induced inflammation.