Journal
JOURNAL OF ORTHOPAEDIC RESEARCH
Volume 32, Issue 9, Pages 1241-1246Publisher
WILEY-BLACKWELL
DOI: 10.1002/jor.22658
Keywords
joint replacement; wear debris; foreign body response; macrophage polarization; lymphocyte
Categories
Funding
- National Doctoral Program of Musculoskeletal Disorders and Biomaterials
- Finnish Research Foundation of Orthopaedics and Traumatology
- Finska Lakaresallskapet
- Research Foundation of the University of Helsinki
- HUS EVO
- Paulo Foundation
- Emil Aaltonen Foundation
- Jane and Aatos Erkko Foundation
- Sigrid Juselius Foundation
- Danish Council for Strategic Research
- European Science Foundation Regenerative Medicine RNP
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Aseptic loosening of hip replacements is driven by the macrophage reaction to wear particles. The extent of particle-induced macrophage activation is dependent on the state of macrophage polarization, which is dictated by the local cytokine microenvironment. The aim of the study was to characterize cytokine microenvironment surrounding failed, loose hip replacements with an emphasis on identification of cytokines that regulate macrophage polarization. Using qRT-PCR, the expression of interferon gamma (IFN-gamma), interleukin-4 (IL-4), granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-13, and IL-17A was low and similar to the expression in control synovial tissues of patients undergoing primary hip replacement. Using immunostaining, no definite source of IFN-gamma or IL-4 could be identified. IL-17A positive cells, identified as mast cells by double staining, were detected but their number was significantly reduced in interface tissues compared to the controls. Significant up-regulation of IL-10, M-CSF, IL-8, CCL2-4, CXCL9-10, CCL22, TRAP, cathepsin K, and down regulation of OPG was seen in the interface tissues, while expression of TNF-alpha, IL-1 beta, and CD206 were similar between the conditions. It is concluded that at the time of the revision surgery the peri-implant macrophage phenotype has both M1 and M2 characteristics and that the phenotype is regulated by other local and systemic factors than traditional macrophage polarizing cytokines. (C) 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
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