title: 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 microm) and ultra high molecular weight polyethylene (UHMWPE, 2-3 microm) 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-1alpha) 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-1alpha, however, more than one chemokine may be necessary for chemotaxis.
authors.affiliation: Orthopaedic Research Laboratory, Stanford University Medical Center, Stanford, California 94305, USA. zhinong@stanford.edu
authors.forename: Zhinong
authors.initials: Z
authors.lastname: Huang
authors.forename: Ting
authors.initials: T
authors.lastname: Ma
authors.forename: Pei-Gen
authors.initials: PG
authors.lastname: Ren
authors.forename: R Lane
authors.initials: RL
authors.lastname: Smith
authors.forename: Stuart B
authors.initials: SB
authors.lastname: Goodman
mesh_terms: D000818:Animals; D001178:Arthroplasty; D018932:Chemokine CCL2 / Q000378:metabolism; D054405:Chemokine CCL3 / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D006801:Humans; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D011095:Polyethylenes / Q000494:pharmacology*; D019904:Polymethyl Methacrylate / Q000494:pharmacology*; D054389:Receptors, CCR1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D054390:Receptors, CCR2 / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D018932:Chemokine CCL2; D054405:Chemokine CCL3; D017077:Culture Media, Conditioned; D011095:Polyethylenes; D054389:Receptors, CCR1; D054390:Receptors, CCR2; C111601:ultra-high molecular weight polyethylene; D019904:Polymethyl Methacrylate