Vascular Endothelial Growth Factor Gene Silencing Suppresses Wear Debris-induced Inflammation

Overview

Journal Int Orthop

Specialty Orthopedics

Date 2011 Apr 9

PMID 21475978

Citations 4

Authors

Wei Zhang

Xiaochun Peng

Tao Cheng

Xianlong Zhang

Affiliations

Soon will be listed here.

Abstract

Purpose: 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.

Methods: 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.

Results: 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).

Conclusions: These findings suggest that local VEGF inhibition might be a promising therapeutic candidate to alleviate particle-induced inflammation.

Citing Articles

Enalapril inhibits inflammatory osteolysis induced by wear debris in a mouse model.

Ma H, Zhang Q, Shi J, Gao Y, Sun C, Zhang W J Int Med Res. 2020; 48(6):300060520931612.

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Are biologic treatments a potential approach to wear- and corrosion-related problems?.

Smith R, Schwarz E Clin Orthop Relat Res. 2014; 472(12):3740-6.

PMID: 24993143 PMC: 4397762. DOI: 10.1007/s11999-014-3765-9.

Protection against titanium particle-induced inflammatory osteolysis by the proteasome inhibitor bortezomib in vivo.

Mao X, Pan X, Zhao S, Peng X, Cheng T, Zhang X Inflammation. 2012; 35(4):1378-91.

PMID: 22391745 DOI: 10.1007/s10753-012-9451-8.

In vitro studies on the effect of particle size on macrophage responses to nanodiamond wear debris.

Thomas V, Halloran B, Ambalavanan N, Catledge S, Vohra Y Acta Biomater. 2012; 8(5):1939-47.

PMID: 22342422 PMC: 3314099. DOI: 10.1016/j.actbio.2012.01.033.

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