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Protective effects of COX-2 inhibitor on titanium-particle-induced inflammatory osteolysis via the down-regulation of RANK/RANKL

Paper ID Volume ID Publish Year Pages File Format Full-Text
1024 71 2011 6 PDF Available
Title
Protective effects of COX-2 inhibitor on titanium-particle-induced inflammatory osteolysis via the down-regulation of RANK/RANKL
Abstract

Particle-wear-induced inflammatory osteolysis remains a major problem for the long-term success of total joint arthroplasty. Previous studies have demonstrated that cyclooxygenase-2 (COX-2) is expressed abundantly in the tissue around a failed implant. However, the role of COX-2 in the development of particle-wear-induced osteoclastogenesis remains unclear. The aim of the study was to test the hypothesis that Dynastat, a COX-2 inhibitor, ameliorates particle-wear-induced inflammatory osteoclastogenesis through the down-regulation of the receptor activators of nuclear factor-κB (RANK) and nuclear factor-κB ligand (RANKL) expression in a murine osteolysis model. Titanium (Ti) particles were introduced into established air pouches in BALB/c mice, followed by the implantation of calvaria bone from syngeneic littermates. Dynastat was given to mice intraperitoneally 2 days before the introduction of Ti particles and maintained until the mice were sacrificed. Pouch tissues were collected 14 days after Ti inoculation for molecular and histological analysis. The results showed that Dynastat has more impact on Ti-particle-induced prostaglandin E2 expression and less on the expression of interleukin-1β and tumor necrosis factor-α. Dynastat inhibited Ti-particle-induced osteoclastogenesis by reducing the gene activation of RANK and RANKL, and diminishing the RANKL expression in Ti-particle-charged pouches. Dynastat markedly reduced the number of tartrate-resistant acid-phosphatase-positive cells in pouch tissues stimulated by Ti particles. In conclusion, this study provides evidence that Dynastat can markedly inhibit Ti-particle-induced osteoclastogenesis by the down-regulation of RANK/RANKL in a murine air pouch model, and is a promising therapeutic candidate for the treatment of inflammatory osteolysis induced by wear particles.

Keywords
Wear particle; Cyclooxygenase-2; Prostaglandin E2; Dynastat; Osteoclastogenesis
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Protective effects of COX-2 inhibitor on titanium-particle-induced inflammatory osteolysis via the down-regulation of RANK/RANKL
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Publisher
Database: Elsevier - ScienceDirect
Journal: Acta Biomaterialia - Volume 7, Issue 8, August 2011, Pages 3216–3221
Authors
, , , , , , , ,
Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us