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Bone-protective effects of nonviral gene therapy with folate-chitosan DNA nanoparticle containing interleukin-1 receptor antagonist gene in rats with adjuvant-induced arthritis.

Authors
  • Fernandes, Julio C1
  • Wang, Huijie
  • Jreyssaty, Christian
  • Benderdour, Mohamed
  • Lavigne, Patrick
  • Qiu, Xingpin
  • Winnik, Francoise M
  • Zhang, Xiaoling
  • Dai, Kerong
  • Shi, Qin
  • 1 Orthopaedics Research Laboratory, Research Center, Sacré-Coeur Hospital, University of Montreal, Montreal, Quebec, Canada.
Type
Published Article
Journal
Molecular Therapy
Publisher
Elsevier
Publication Date
July 2008
Volume
16
Issue
7
Pages
1243–1251
Identifiers
DOI: 10.1038/mt.2008.99
PMID: 18500247
Source
Medline
License
Unknown

Abstract

Interleukin-1 receptor antagonist (IL-1Ra), is a natural blocker of the inflammatory cytokine interleukin-1. Using a rat adjuvant-induced arthritis (AIA) model of rheumatoid arthritis (RA), we examined the protective effects of IL-1Ra in bone metabolism in vivo after folate-mediated nonviral gene delivery. We detected secreted human IL-1Ra protein in serum and cultured primary osteoblasts of rats that were treated with chitosan-IL-1Ra and folate-IL-1Ra-chitosan nanoparticles, respectively. In vivo, IL-1Ra gene delivery significantly reverted alterations in bone turnover observed in arthritic animals by modulating the level of osteocalcin (OC) as well as the activities of alkaline phosphatase and tartrate-resistant acid phosphatase. The protective effects of these nanoparticles were evident from the decrease in the expression levels of interleukine-1beta and prostaglandin E(2) as well as osteoclast number and other histopathological findings. Compared to naked DNA and chitosan-DNA, folate-chitosan-DNA nanoparticles were less cytotoxic and enhanced IL-1Ra protein synthesis in vitro and offered a better protection against inflammation and abnormal bone metabolism in vivo. Nonviral gene therapy with folate-chitosan-DNA nanoparticles containing the IL-1 Ra gene seemed to protect against bone damage and inflammation in rat adjuvant-induced arthritis model.

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