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Authors Wang S, Wei X, Sun X, Chen C, Zhou J, Zhang G, Wu H, Guo B, Wei L
Received 28 May 2017
Accepted for publication 22 November 2017
Published 31 January 2018 Volume 2018:13 Pages 617—631
DOI https://doi.org/10.2147/IJN.S142797
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Akshita Wason
Peer reviewer comments 3
Editor who approved publication: Dr Linlin Sun
Background: Cartilage degeneration affects millions of people but preventing
its degeneration is a big challenge. Although RNA interference (RNAi) has been
used in human trials via silencing specific genes, the cartilage RNAi has not
been possible to date because the cartilage is an avascular and very dense
tissue with very low permeability.
Purpose: The objective of this study was to develop and
validate a novel lipid nanoparticle (LNP)-siRNA delivery system that can
prevent cartilage degeneration by knocking down specific genes.
Methods: LNP transfection efficiency was evaluated in
vitro and ex vivo. Indian Hedgehog (Ihh ) has been
correlated with cartilage degeneration. The in vivo effects of LNP-Ihh siRNA
complexes on cartilage degeneration were evaluated in a rat model of
surgery-induced osteoarthritis (OA).
Results: In vitro, 100% of chondrocytes were transfected
with siRNA in the LNP-siRNA group. In accordance with the cell culture results,
red positive signals could be detected even in the deep layer of cartilage
tissue cultures treated by LNP-beacon. In vivo data showed that LNP is specific
for cartilage, since positive signals were detected by fluorescence molecular
tomography and confocal microscopy in joint cartilage injected with LNP-beacon,
but not on the surface of the synovium. In the rat model of OA, intraarticular
injection of LNP-Ihh siRNA attenuated OA progression, and PCR results showed
LNP-Ihh siRNA exerted a positive impact on anabolic metabolism and negative
impact on catabolic metabolism.
Conclusion: This study demonstrates that our LNP-RNAi
delivery system has a significantly chondroprotective effect that attenuates
cartilage degeneration and holds great promise as a powerful tool for treatment
of cartilage diseases by knocking down specific genes.
Keywords: cartilage
diseases, lipid nanoparticle, RNA interference, delivery system