Abstract
Background: Aseptic loosening remains the most common cause of failure of total hip arthroplasty. Its pathogenesis is based upon the generation of wear debris particles which trigger synovial macrophage activation.
Statins, inhibitors of 3-hydroxy-3 methylglutaryl coenzyme A (HMG-Co-A) reductase, have revolutionised the treatment of hypercholesterolaemia. More recently statins have been shown to have potent anti inflammatory effects. We investigated the effects of cerivastatin in attenuating the activation of human macrophages by polymethylmethacrylate (PMMA) particles.
Methods: Polymethylmethacrylate-particle-stimulated human macrophages were cultured in vitro with cerivastatin at 75 and 150... mols/litre. TNF-α (tumour necrosis factor alpha) and MCP-1 (monocyte chemotactic protein) expression were determined using ELISA. An ERK1/2 inhibitor, UO126 was utilised to identify the mitogen activated protein kinase (MAP-Kinase) pathway involved and western blotting was used to demonstrate the effect of Cerivastatin on this pathway.
Results PMMA-stimulated TNF-α and MCP-1 expression was consistently attenuated by cerivastatin therapy.
PMMA activation was attenuated by the ERK1/2 inhibitor, UO126.
Western blotting confirmed ERK downregulation by cerivastatin, establishing a mechanism for its anti-inflammatory effects.
Conclusion: We have demonstrated the beneficial effects of statins in suppressing particle mediated activation of macrophages and the potential to prevent or treat periprosthetic osteolysis.
The abstracts were prepared by Emer Agnew, Secretary to the IOA. Correspondence should be addressed to him at Irish Orthopaedic Association Secretariat, c/o Cappagh National Orthopaedic Hospital, Finglas, Dublin 11, Ireland.
