Peer-Reviewed Journal Details
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Laing, AJ,Dillon, JP,Mulhall, KJ,Wang, JH,McGuinness, AJ,Redmond, PH
2008
August
Acta Orthopaedica
Statins attenuate polymethylmethacrylate-mediated monocyte activation
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Optional Fields
DEBRIS-INDUCED OSTEOLYSIS TOTAL HIP-ARTHROPLASTY NECROSIS-FACTOR-ALPHA KAPPA-B ACTIVATION BONE-RESORPTION POLYETHYLENE PARTICLES CHEMOKINE EXPRESSION MONONUCLEAR-CELLS BLOOD MONOCYTES JOINT FLUID
79
134
140
Background 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- 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- 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.
DOI 10.1080/17453670710014888
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