Aseptic loosening and periprosthetic osteolysis resulting from wear debris are major complications of total joint arthroplasty. Monocyte/macrophages are the key cells related to osteolysis at the bone-implant interface of joint arthroplasties. Whether the monocyte/macrophages found at the implant interface in the presence of polyethylene particles are locally or systemically derived is unknown.
We therefore asked (1) whether macrophages associated with polyethylene particle-induced chronic inflammation are recruited locally or systemically and (2) whether the recruited macrophages are associated with enhanced osteolysis locally.
Noninvasive in vivo imaging techniques (bioluminescence and microCT) were used to investigate initial macrophage migration systemically from a remote injection site to polyethylene wear particles continuously infused into the femoral canal. We used histologic and immunohistologic staining to confirm localization of migrated macrophages to the polyethylene particle-treated femoral canals and monitor cellular markers of bone remodeling.
The values for bioluminescence were increased for animals receiving UHMWPE particles compared with the group in which the carrier saline was infused. At Day 8, the ratio of bioluminescence (operated femur divided by nonoperated contralateral femur of each animal) for the UHMWPE group was 13.95 ± 5.65, whereas the ratio for the saline group was 2.60 ± 1.14. Immunohistologic analysis demonstrated the presence of reporter macrophages in the UHMWPE particle-implanted femora only. MicroCT scans showed the bone mineral density for the group with both UHMWPE particles and macrophage was lower than the control groups.
Infusion of clinically relevant polyethylene particles, similar to the human scenario, stimulated systemic migration of remotely injected macrophages and local net bone resorption.
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We thank Dr Afraaz Irani for performing the bone mineral density analysis of the microCT scans. We thank Dr Gobalakrishnan Sundaresan who supplied the Fluc and GFP expressing RAW264.7 macrophage cell line, Dr Timothy Wright (Hospital for Special Surgery, New York, NY) who supplied the UHMWPE particles, and Stephanie Byun for sectioning of samples used in this study. We also thank Dr Lane Smith, Dr Sam Gambhir, and Dr Chris Contag for their helpful advice.
One or more of the authors (SBG, SB, TM, P-GR) have received funding from the National Institutes of Health, National Institute of Arthritis, Musculoskeletal and Skin Diseases, Grant #1R01AR055650 in support of this study.
Each author certifies that his or her institution has approved the animal protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research.
This work was performed at the Orthopaedic Research Laboratories and the Stanford Small Animal Imaging Facility at the Clarke Center at Stanford University, Stanford, CA, USA.
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Ren, PG., Irani, A., Huang, Z. et al. Continuous Infusion of UHMWPE Particles Induces Increased Bone Macrophages and Osteolysis. Clin Orthop Relat Res 469, 113–122 (2011). https://doi.org/10.1007/s11999-010-1645-5
- Bone Mineral Density
- Wear Debris
- Wear Particle
- Total Joint Arthroplasty