Effects of orthopedic polymer particles on chemotaxis of macrophages and mesenchymal stem cells

Abstract

Wear particles generated from total joint arthroplasty (TJA) stimulate macrophages to release chemokines. The role of chemokines released from wear particle-stimulated macrophages on the migration of macrophages and osteoprogenitor cells in vitro has not been elucidated. In this study, we challenged murine macrophages (RAW 264.7) with clinically relevant polymethyl methacrylate (PMMA, 1-10 μm) and ultra high molecular weight polyethylene (UHMWPE, 2-3 μm) particles. The chemotactic effects of the conditioned media (CM) were tested in vitro using human macrophages (THP-1) and human mesenchymal stem cells (MSCs) as the migrating cells. CM collected from both particle types had a chemotactic effect on human macrophages, which could be eliminated by monocyte chemotactic protein-1 (MCP-1) neutralizing antibody. Blocking the CCR1 receptor eliminated the chemotactic effect, while CCR2 antibody only partially decreased THP-1 cell migration. CM from PMMA but not UHMWPE-exposed macrophages led to chemotaxis of MSCs; this effect could be eliminated by macrophage inflammatory protein-1 alpha (MIP-1α) neutralizing antibody. Neither CCR1 nor CCR2 blocking antibodies showed an effect on the migration of MSCs. Chemokines released by macrophages stimulated by wear particles can have an effect on the migration of macrophages and MSCs. This effect seems to be dependent on the particle type, and may be modulated by MCP-1 and MIP-1α, however more than one chemokine may be necessary for chemotaxis.

Mutant monocyte chemoattractant protein 1 protein attenuates migration of and inflammatory cytokine release by macrophages exposed to orthopedic implant wear particles

“…The methodology for the chemotaxis experiments reported herein were originally developed and reported by Huang et al 14 from our laboratory. In the migration experiments, human macrophages were used as the migrating cells due to their high sensitivity to chemotactic cytokines.…”

Exogenous MC3T3 Preosteoblasts Migrate Systemically and Mitigate the Adverse Effects of Wear Particles

“…To this end, it has recently been shown that polymethyl methacrylate particle-conditioned media induced migration of MSCs, an effect that was blocked by neutralizing the macrophage inflammatory protein-1a (MIP-1a), a chemokine also known to attract monocyte/macrophages. 17 These preliminary results suggest that some of the same chemokines that recruit circulating monocytes/macrophages could also recruit osteoprogenitor cells.…”

Tribological interactions of polyethylene in total hip arthroplasty (THA)

“…Endothelial cells recruit circulating cells, as monocytes 8.1 Infl ammatory process activated by polymeric debris and mediated by macrophages, leading to soft tissue damage and bone resorption. and lymphocytes, through a chemo-attractive mechanism mediated by MCP-1, MIP-1 and IL-8, to their surface: these cells roll along the endothelial cells, to extravasate and reach the reactive site (Huang et al , 2010). In addition to monocytes, lymphocytes have been shown to differentiate into osteoclasts (Roato et al , 2010).…”