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dc.contributor.authorLaing, Alan J
dc.contributor.authorDillon, John P
dc.contributor.authorMulhall, Kevin J
dc.contributor.authorWang, J H
dc.contributor.authorMcGuinness, Anthony J
dc.contributor.authorRedmond, Paul H
dc.date.accessioned2012-02-03T15:13:40Z
dc.date.available2012-02-03T15:13:40Z
dc.date.issued2012-02-03T15:13:40Z
dc.identifier.citationActa Orthop. 2008 Feb;79(1):134-40.en_GB
dc.identifier.issn1745-3682 (Electronic)en_GB
dc.identifier.issn1745-3674 (Linking)en_GB
dc.identifier.pmid18283585en_GB
dc.identifier.doi10.1080/17453670710014888en_GB
dc.identifier.urihttp://hdl.handle.net/10147/209153
dc.description.abstractBACKGROUND: Periprosthetic osteolysis precipitates aseptic loosening of components, increases the risk of periprosthetic fracture and, through massive bone loss, complicates revision surgery and ultimately is the primary cause for failure of joint arthroplasty. The anti-inflammatory properties of HMG-CoA reductase inhibitors belonging to the statin family are well recognized. We investigated a possible role for status in initiating the first stage of the osteolytic cycle, namely monocytic activation. METHODS: We used an in vitro model of the human monocyte/macrophage inflammatory response to poly-methylmethacrylate (PMMA) particles after pretreat-ing cells with cerivastatin, a potent member of the statin family. Cell activation based upon production of TNF-alpha and MCP-1 cytokines was analyzed and the intracellular Raf-MEK-ERK signal transduction pathway was evaluated using western blot analysis, to identify its role in cell activation and in any cerivastatin effects observed. RESULTS: We found that pretreatment with cerivastatin significantly abrogates the production of inflammatory cytokines TNF-alpha and MCP-1 by human monocytes in response to polymethylmethacrylate particle activation. This inflammatory activation and attenuation appear to be mediated through the intracellular Raf-MEK-ERK pathway. INTERPRETATION: We propose that by intervening at the upstream activation stage, subsequent osteoclast activation and osteolysis can be suppressed. We believe that the anti-inflammatory properties of statins may potentially play a prophylactic role in the setting of aseptic loosening, and in so doing increase implant longevity.
dc.language.isoengen_GB
dc.subject.meshAnti-Inflammatory Agents/*pharmacologyen_GB
dc.subject.meshArthroplasty, Replacement/adverse effectsen_GB
dc.subject.meshCytokines/biosynthesisen_GB
dc.subject.meshHumansen_GB
dc.subject.meshHydroxymethylglutaryl-CoA Reductase Inhibitors/*pharmacologyen_GB
dc.subject.meshInflammation/immunologyen_GB
dc.subject.meshModels, Biologicalen_GB
dc.subject.meshMonocytes/*drug effects/immunologyen_GB
dc.subject.meshOsteolysis/etiology/immunologyen_GB
dc.subject.meshPolymethyl Methacrylate/*pharmacologyen_GB
dc.subject.mesh*Prosthesis Failureen_GB
dc.subject.meshPyridines/*pharmacologyen_GB
dc.titleStatins attenuate polymethylmethacrylate-mediated monocyte activation.en_GB
dc.contributor.departmentDepartment of Surgical Research, Cork University Hospital, Cork, Ireland., alanjlaing1@hotmail.comen_GB
dc.identifier.journalActa orthopaedicaen_GB
dc.description.provinceMunster
html.description.abstractBACKGROUND: Periprosthetic osteolysis precipitates aseptic loosening of components, increases the risk of periprosthetic fracture and, through massive bone loss, complicates revision surgery and ultimately is the primary cause for failure of joint arthroplasty. The anti-inflammatory properties of HMG-CoA reductase inhibitors belonging to the statin family are well recognized. We investigated a possible role for status in initiating the first stage of the osteolytic cycle, namely monocytic activation. METHODS: We used an in vitro model of the human monocyte/macrophage inflammatory response to poly-methylmethacrylate (PMMA) particles after pretreat-ing cells with cerivastatin, a potent member of the statin family. Cell activation based upon production of TNF-alpha and MCP-1 cytokines was analyzed and the intracellular Raf-MEK-ERK signal transduction pathway was evaluated using western blot analysis, to identify its role in cell activation and in any cerivastatin effects observed. RESULTS: We found that pretreatment with cerivastatin significantly abrogates the production of inflammatory cytokines TNF-alpha and MCP-1 by human monocytes in response to polymethylmethacrylate particle activation. This inflammatory activation and attenuation appear to be mediated through the intracellular Raf-MEK-ERK pathway. INTERPRETATION: We propose that by intervening at the upstream activation stage, subsequent osteoclast activation and osteolysis can be suppressed. We believe that the anti-inflammatory properties of statins may potentially play a prophylactic role in the setting of aseptic loosening, and in so doing increase implant longevity.


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