What are the local and systemic biologic reactions and mediators to wear debris, and what host factors determine or modulate the biologic response to wear particles?

Abstract

New clinical and basic science data on the cellular and molecular mechanisms by which wear particles stimulate the host inflammatory response have provided deeper insight into the pathophysiology of periprosthetic bone loss. Interactions among wear particles, macrophages, osteoblasts, bone marrow-derived mesenchymal stem cells, fibroblasts, endothelial cells, and T cells contribute to the production of pro-inflammatory and pro-osteoclastogenic cytokines such as TNF-alpha, RANKL, M-SCF, PGE2, IL-1, IL-6, and IL-8. These cytokines not only promote osteoclastogenesis but interfere with osteogenesis led by osteoprogenitor cells. Recent studies indicate that genetic variations in TNF-alpha, IL-1, and FRZB can result in subtle changes in gene function, giving rise to altered susceptibility or severity for periprosthetic inflammation and bone loss. Continuing research on the biologic effects and mechanisms of action of wear particles will provide a rational basis for the development of novel and effective ways of diagnosis, prevention, and treatment of periprosthetic inflammatory bone loss.

Figure 1

Biologic reactions between wear debris and host cells. IL = interleukin, MCP = monocyte chemoattractant protein, M-CSF = macrophage colony–stimulating factor, MIP = macrophage inflammatory protein, NFκB = nuclear factor κB, RANKL = receptor activator of nuclear factor κB ligand, TLR = toll-like receptor, TNF = tumor necrosis factor

Figure 2

Interaction between antigen-presenting cells (APC) and T cells. CTLA = cytotoxic T-lymphocyte antigen, ICAM = intercellular adhesion molecule, IFN = interferon, IL = interleukin, LFA = lymphocyte function-associated antigen, MHC = major histocompatibility index, TCR = T-cell receptor, TNF = tumor necrosis factor