Abstract
The destruction of bone around joint replacements (periprosthetic osteolysis) is an adverse biological response associated with the generation of excessive wear particles. Wear debris from the materials used for joint replacements stimulate a chronic inflammatory and foreign body reaction that leads to increased osteoclast differentiation and maturation, and decreased bone formation. Wear debris induces both local and systemic trafficking of inflammatory cells to the site of particle generation. Recent studies have shown that this effect is mediated primarily by chemotactic cytokines (chemokines) including macrophage chemotactic protein-1 (MCP-1, also known as CCL2), macrophage inhibitory protein-1 (MIP-1), Interleukin-8 (IL-8 or CXCL8) and others. These ligands migrate along a concentration gradient to interact with G-protein-linked transmembrane receptors on the cell surface. Chemokines are involved in the innate and adaptive immune responses, angiogenesis, wound healing and tissue repair. In vitro, in vivo and tissue retrieval studies have shown that chemokine-directed systemic trafficking of polymorphonuclear leukocytes and cells of the monocyte/macrophage lineage to wear particles result in the release of pro-inflammatory factors and subsequent bone loss. Modulation of the chemokine ligand-receptor axis is a potential strategy to mitigate the adverse effects of wear particles from joint replacements.