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The effect of Lipoxin A(4 )on the interaction between macrophage and osteoblast: possible role in the treatment of aseptic loosening
BACKGROUND: Aseptic loosening (AL) is the main problem of total joints replacement (TJR) by the implantation of permanently prosthetic components. In vitro and in vivo studies have clearly demonstrated that wear debris and its byproducts could trigger inflammation in the peri-implant tissue. Lipoxin...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2698870/ https://www.ncbi.nlm.nih.gov/pubmed/19490628 http://dx.doi.org/10.1186/1471-2474-10-57 |
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author | Li, Gang Wu, Ping Xu, Yao Yu, Yan Sun, Li Zhu, Liang Ye, Duyun |
author_facet | Li, Gang Wu, Ping Xu, Yao Yu, Yan Sun, Li Zhu, Liang Ye, Duyun |
author_sort | Li, Gang |
collection | PubMed |
description | BACKGROUND: Aseptic loosening (AL) is the main problem of total joints replacement (TJR) by the implantation of permanently prosthetic components. In vitro and in vivo studies have clearly demonstrated that wear debris and its byproducts could trigger inflammation in the peri-implant tissue. Lipoxins (LXs) are endogenous eicosanoids synthesized locally from arachidonate acid (AA) at sites of inflammation and mediate pro-resolving activity. A number of studies have demonstrated the effect of LXA(4 )to counteract inflammation in different cell and animal models, but till now, no relative report about the role of LXs in progress or prevention of AL. METHODS: Murine RAW264.7 macrophage cell line and MC3T3-E1 osteoblasts (OB) cell line were purchased. Co-cultured model of these two cell lines was established. To explore the effect of exogenous Lipoxin A(4 )(LXA(4)) on polymethylmethacrylate (PMMA) induced inflammation, pro-inflammatory cytokines including TNF-α, IL-1β, PGE(2 )and GM-CSF were measured by ELISA kits and bone resorption was quantified by measuring calcium release from 5-day-old mice calvaria in vitro. To determine further the endogenous effect of LXA(4), cells were co-cultured and with or without 15-lipoxygease (15-LO) blocking by 15-LO siRNA. Both real-time PCR and western blotting were applied to confirm the inhibitory efficiency of 15-LO by siRNA. RESULTS: 0.1 mg/ml, 0.5 mg/ml and 1.0 mg/ml PMMA showed a time-dependent manner to trigger production of all the pro-inflammatory cytokines studied. Exogenous 0–100 nM LXA(4 )presented an inhibitory effect on both generation of above cytokines and PMMA stimulated calvarial bone resorption with a dose-dependent manner. LXA(4 )in supernatant from neither rest macrophages nor macrophages cultured alone exposing to PMMA was detectable. In co-cultured cells challenged by PMMA, LXA(4 )was increased significantly, while, this enhance could be partly inhibited by 15-LO siRNA. When LXA(4 )generation was blocked with 15-LO siRNA, the PMMA induced pro-inflammatory cytokines were elevated and bone resorption was accelerated. CONCLUSION: In the present study, we demonstrated that LXA(4 )had a favorable inhibitory effect on PMMA-induced inflammation in a macrophage and OB co-culture system. |
format | Text |
id | pubmed-2698870 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-26988702009-06-19 The effect of Lipoxin A(4 )on the interaction between macrophage and osteoblast: possible role in the treatment of aseptic loosening Li, Gang Wu, Ping Xu, Yao Yu, Yan Sun, Li Zhu, Liang Ye, Duyun BMC Musculoskelet Disord Research Article BACKGROUND: Aseptic loosening (AL) is the main problem of total joints replacement (TJR) by the implantation of permanently prosthetic components. In vitro and in vivo studies have clearly demonstrated that wear debris and its byproducts could trigger inflammation in the peri-implant tissue. Lipoxins (LXs) are endogenous eicosanoids synthesized locally from arachidonate acid (AA) at sites of inflammation and mediate pro-resolving activity. A number of studies have demonstrated the effect of LXA(4 )to counteract inflammation in different cell and animal models, but till now, no relative report about the role of LXs in progress or prevention of AL. METHODS: Murine RAW264.7 macrophage cell line and MC3T3-E1 osteoblasts (OB) cell line were purchased. Co-cultured model of these two cell lines was established. To explore the effect of exogenous Lipoxin A(4 )(LXA(4)) on polymethylmethacrylate (PMMA) induced inflammation, pro-inflammatory cytokines including TNF-α, IL-1β, PGE(2 )and GM-CSF were measured by ELISA kits and bone resorption was quantified by measuring calcium release from 5-day-old mice calvaria in vitro. To determine further the endogenous effect of LXA(4), cells were co-cultured and with or without 15-lipoxygease (15-LO) blocking by 15-LO siRNA. Both real-time PCR and western blotting were applied to confirm the inhibitory efficiency of 15-LO by siRNA. RESULTS: 0.1 mg/ml, 0.5 mg/ml and 1.0 mg/ml PMMA showed a time-dependent manner to trigger production of all the pro-inflammatory cytokines studied. Exogenous 0–100 nM LXA(4 )presented an inhibitory effect on both generation of above cytokines and PMMA stimulated calvarial bone resorption with a dose-dependent manner. LXA(4 )in supernatant from neither rest macrophages nor macrophages cultured alone exposing to PMMA was detectable. In co-cultured cells challenged by PMMA, LXA(4 )was increased significantly, while, this enhance could be partly inhibited by 15-LO siRNA. When LXA(4 )generation was blocked with 15-LO siRNA, the PMMA induced pro-inflammatory cytokines were elevated and bone resorption was accelerated. CONCLUSION: In the present study, we demonstrated that LXA(4 )had a favorable inhibitory effect on PMMA-induced inflammation in a macrophage and OB co-culture system. BioMed Central 2009-06-02 /pmc/articles/PMC2698870/ /pubmed/19490628 http://dx.doi.org/10.1186/1471-2474-10-57 Text en Copyright © 2009 Li et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Li, Gang Wu, Ping Xu, Yao Yu, Yan Sun, Li Zhu, Liang Ye, Duyun The effect of Lipoxin A(4 )on the interaction between macrophage and osteoblast: possible role in the treatment of aseptic loosening |
title | The effect of Lipoxin A(4 )on the interaction between macrophage and osteoblast: possible role in the treatment of aseptic loosening |
title_full | The effect of Lipoxin A(4 )on the interaction between macrophage and osteoblast: possible role in the treatment of aseptic loosening |
title_fullStr | The effect of Lipoxin A(4 )on the interaction between macrophage and osteoblast: possible role in the treatment of aseptic loosening |
title_full_unstemmed | The effect of Lipoxin A(4 )on the interaction between macrophage and osteoblast: possible role in the treatment of aseptic loosening |
title_short | The effect of Lipoxin A(4 )on the interaction between macrophage and osteoblast: possible role in the treatment of aseptic loosening |
title_sort | effect of lipoxin a(4 )on the interaction between macrophage and osteoblast: possible role in the treatment of aseptic loosening |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2698870/ https://www.ncbi.nlm.nih.gov/pubmed/19490628 http://dx.doi.org/10.1186/1471-2474-10-57 |
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