Cationic solid lipid nanoparticles loaded by integrin β1 plasmid DNA attenuates IL-1β-induced apoptosis of chondrocyte.

Yuejiang Zhao,Lu Wang,Shijie Liu,Simin Luo,Zhiyuan Guo,Hanwen Chen

doi:10.18632/aging.103656

Abstract

Aging-related inflammation is tightly linked with the development of osteoarthritis (OA). As the pro-inflammatory cytokine, IL-1β has been associated with physical dysfunction and frailty. It is still elusive whether and how IL-1β blockade improves the outcome of OA. Here we develop a cationic solid lipid nanoparticles (SLNs) system that effectively mediate non-viral delivery of plasmid DNA (pDNA) into cells. Compared with other DNA transfer technologies including lipofetamin 2000, SLNs-pDNA system is less toxic and exerts identical effectiveness on DNA transfer. Loaded with integrin β1 overexpression pDNA, the SLNs-pDNA mainly localized in cytoplasm and enforced expression of integrin β1 in rat chondrocytes. Moreover, upon exposure to IL-1β stimulation, SLNs-pDNA treatment attenuates the apoptosis rat chondrocytes and augments tissue repair. Our data thus demonstrate that SLNs-pDNA functions as a potential therapeutic nanomedicine in the treatment of osteoarthritis.

Highlights

As a degenerative inflammatory disease, osteoarthritis (OA) is a common and frequently-occurring articular cartilage disease in the elderly, and usually responsible for joint pain and high rates of disability [1]
We have developed a novel gene transfer system, solid lipid nanoparticles (SLNs)-plasmid DNA (pDNA)
Penumarthi A et al have reported that pDNA-loaded SLNs show low cytotoxicity and high transfection efficiency comparable to lipofectamine in dendritic cells [17]

Summary

Introduction

As a degenerative inflammatory disease, osteoarthritis (OA) is a common and frequently-occurring articular cartilage disease in the elderly, and usually responsible for joint pain and high rates of disability [1]. It is characterized by cartilage degenerative damage, such as the degradation of the cartilage matrix and the death of chondrocytes [2]. As a type of important surface adhesion receptors, integrin mainly mediate the adhesion between cells and ECM, and regulate various cell physiological processes, including growth, differentiation, proliferation, adhesion, and apoptosis [9,10,11]. Few studies have evaluated www.aging-us.com whether integrin β1 can be a potential target for OA progression

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