Revision joint replacement, wear particles, and macrophage polarization

Currently, younger, more active patients are being offered total joint replacement (TJR) for end-stage arthritic disorders. Despite improved durability of TJRs, particle-associated wear of the bearing surfaces continues to be associated with particulate debris, which can activate monocyte/macrophages. Activated macrophages then produce pro-inflammatory factors and cytokines that induce an inflammatory reaction that activates osteoclasts leading to bone breakdown and aseptic loosening. We hypothesized that activated macrophages in tissues harvested from revised joint replacements predominantly express an M1 pro-inflammatory phenotype due to wear-particle-associated cell activation, rather than an M2 anti-inflammatory phenotype. We further questioned whether it is possible to convert uncommitted monocyte/macrophages to an M2 phenotype by the addition of interleukin-4 (IL-4), or whether it is necessary to first pass through an M1 intermediate stage. Retrieved periprosthetic tissues demonstrated increased M1/M2 macrophage ratios compared to non-operated osteoarthritic synovial tissues, using immunohistochemical staining and Western blotting. Uncommitted monocyte/macrophages with/without polymethyl-methacrylate particles were transformed to an M2 phenotype by IL-4 more efficiently when the cells were first passed through an M1 phenotype by exposure to endotoxin. Wear particles induce a pro-inflammatory microenvironment that facilitates osteolysis; these events may potentially be modulated favorably by exposure to IL-4.