Effect of etidronate on COX-2 expression and PGE2 production in macrophage-like RAW 264.7 cells stimulated by titanium particles View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2007-11-30

AUTHORS

Yoshihiro Suzuki, Takayuki Nishiyama, Keiichiro Hasuda, Takaaki Fujishiro, Takahiro Niikura, Shinya Hayashi, Shingo Hashimoto, Masahiro Kurosaka

ABSTRACT

BackgroundThe most common failure of total joint replacement is aseptic loosening in association with osteolysis. Previous reports have shown that prostaglandin E2 (PGE2) secreted from macrophages that phagocytosed wear debris induced periprosthetic osteolysis. Many clinical studies have reported that bisphosphonate therapy reduced periprosthetic bone loss and loosening of the implants after total joint replacements. Bisphosphonates are synthetic compounds with the ability to decrease bone resorption. In addition, some bisphosphonates have been reported to have anti-inflammatory effects by reducing the secretion of pro-inflammatory cytokines. However, the mechanism of bisphosphonates that reduces periprosthetic bone resorption remains unclear. The purpose of this study was to investigate one of the mechanisms by which etidronate (EHDP) inhibits periprosthetic bone resorption.MethodsMacrophage-like RAW 264.7 cells were treated with EHDP at concentrations of 0.001, 0.01, 0.1, 1, 10, and 100 µM together with the titanium particles at a concentration of 1 mg/ml. After a 24-h culture period, total mRNA was isolated and reverse transcription-polymerase chain reaction (RT-PCR) was done to examine the expression of cyclooxygenase-2 (COX-2). The supernatants were also collected and production of PGE2, interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were quantified using an enzyme-linked immunosorbent assay (ELISA).ResultsAnalyses showed that COX-2 expression and PGE2 production were suppressed by EHDP in a dose-dependent manner. By 100 µM of EHDP, PGE2 production of the cells was suppressed approximately to the level of the nonstimulated cells. Production of IL-1β, IL-6, and TNF-α in the supernatant was also suppressed by EHDP.ConclusionsThe blockage effect of pro-inflammatory cytokines is a possible etidronate mechanism that reduces bone resorption around implants. More... »

PAGES

568-577

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00776-007-1180-8

DOI

http://dx.doi.org/10.1007/s00776-007-1180-8

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1042746283

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/18040640


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63 culture period
64 cyclooxygenase-2
65 cytokines
66 debris
67 dose-dependent manner
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70 enzyme-linked immunosorbent assay
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73 expression
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75 factors
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78 implants
79 interleukin-1β
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81 joint replacement
82 levels
83 loosening
84 loss
85 mRNA
86 macrophage-like RAW 264.7 cells
87 macrophages
88 manner
89 mechanism
90 mechanisms of bisphosphonates
91 necrosis factor
92 osteolysis
93 particles
94 period
95 periprosthetic bone loss
96 periprosthetic bone resorption
97 periprosthetic osteolysis
98 possible etidronate mechanism
99 previous reports
100 pro-inflammatory cytokines
101 production
102 production of PGE2
103 prostaglandin E2
104 purpose
105 reaction
106 replacement
107 report
108 resorption
109 secretion
110 study
111 supernatant
112 synthetic compounds
113 therapy
114 titanium particles
115 total joint replacement
116 total mRNA
117 transcription-polymerase chain reaction
118 tumor necrosis factor
119 wear debris
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