Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-11-14
pubmed:abstractText
Aseptic loosening is the most common long-term complication of total joint replacement, which is associated with the generation of wear debris. The purpose of this study was to investigate the inhibitory effect of small interfering RNA (siRNA) targeting tumor necrosis factor-alpha (TNF-alpha) on wear debris-induced inflammation. A local delivery of lentivirus-mediated TNF-alpha siRNA into the modified murine air pouch, which was stimulated by polymethylmethacrylate (PMMA) particles, resulted in significant blockage of TNF-alpha both in mRNA and protein levels for up to 4 weeks. In addition, significant down-regulation of interleukin-1 (IL-1) and interleukin-6 (IL-6) was observed in TNF-alpha siRNA-treated pouches. The safety profile of gene therapy was proven by Bioluminescent assay and quantitative fluorescent flux. Histological analysis revealed less inflammatory responses (thinner pouch membrane and decreased cellular infiltration) in TNF-alpha siRNA-treated pouches. These findings suggest that local delivery of TNF-alpha siRNA might be an excellent therapeutic candidate to inhibit particle-induced inflammation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1090-2104
pubmed:author
pubmed:issnType
Electronic
pubmed:day
12
pubmed:volume
377
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
532-7
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Efficient Inhibition of wear debris-induced inflammation by locally delivered siRNA.
pubmed:affiliation
Department of Orthopaedics, The Sixth Affiliated People's Hospital, Shanghai Jiaotong University, 600 Yishan Road, Shanghai 200233, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't