Efficient Inhibition of wear debris-induced inflammation by locally delivered siRNA
- Department of Orthopaedics, Sixth Affiliated People's Hospital, Shanghai Jiaotong University, 600 Yishan Road, Shanghai 200233 (China)
- Department of Orthopaedics, Sixth Ningbo Hospital, East Zhongshan Road, Ningbo 315040 (China)
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.
- OSTI ID:
- 21255782
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 377, Issue 2; Other Information: DOI: 10.1016/j.bbrc.2008.10.026; PII: S0006-291X(08)01975-X; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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