Over-expression of receptor activator of nuclear factor-kappaB ligand (RANKL), inflammatory cytokines, and chemokines in periprosthetic osteolysis of loosened total hip arthroplasty

Abstract

Loosening of total hip arthroplasty (THA) caused by periprosthetic osteolysis induced by ultra-high molecular weight polyethylene (UHMWPE) particles is a major clinical problem. We investigated whether there are differences between loosened THA patients and primary THA patients in (1) receptor activator of nuclear factor-kappaB ligand (RANKL) expression on periprosthetic bone marrow cells; (2) RANKL levels, osteoprotegerin (OPG)/RANKL ratios, the levels of inflammatory cytokines and chemokines in synovial fluid. We used flow cytometric analysis to detect RANKL expression on periprosthetic bone marrow cells. We used enzyme-linked immunoassay and multiplex microsphere-based immunoassay to measure RANKL, OPG, cytokines, and chemokines in synovial fluid. We found loosened THA patients had higher RANKL expression on osteoblastic stromal cells, higher levels of RANKL, interleukin (IL)-6, IL-8, IL-10, interferon-gamma-inducible protein (IP)-10, monocyte chemoattractant protein (MCP)-1, monokine induced by interferon-gamma (MIG), and lower OPG/RANKL ratios in synovial fluid than primary THA patients. There was positive correlation between the levels of IL-6, IL-8, IL-10, IP-10, MCP-1, or MIG and RANKL levels in synovial fluid or RANKL expression on osteoblastic stromal cells. These suggest that UHMWPE particles induce over-expression of RANKL, IL-6, IL-8, IP-10, MCP-1, and MIG in human periprosthetic microenvironment. This results in periprosthetic osteolysis and loosening of THA.