title: Biological responses of human mesenchymal stem cells to titanium wear debris particles.
abstract: Wear debris-induced osteolysis is a major cause of orthopedic implant aseptic loosening, and various cell types, including macrophages, monocytes, osteoblasts, and osteoclasts, are involved. We recently showed that mesenchymal stem/osteoprogenitor cells (MSCs) are another target, and that endocytosis of titanium (Ti) particles causes reduced MSC proliferation and osteogenic differentiation. Here we investigated the mechanistic aspects of the endocytosis-mediated responses of MSCs to Ti particulates. Dose-dependent effects were observed on cell viability, with doses >300 Ti particles/cell resulting in drastic cell death. To maintain cell viability and analyze particle-induced effects, doses <300 particles/cell were used. Increased production of interleukin-8 (IL-8), but not IL-6, was observed in treated MSCs, while levels of TGF-β, IL-1β, and TNF-α were undetectable in treated or control cells, suggesting MSCs as a likely major producer of IL-8 in the periprosthetic zone. Disruptions in cytoskeletal and adherens junction organization were also observed in Ti particles-treated MSCs. However, neither IL-8 and IL-6 treatment nor conditioned medium from Ti particle-treated MSCs failed to affect MSC osteogenic differentiation. Among other Ti particle-induced cytokines, only GM-CSF appeared to mimic the effects of reduced cell viability and osteogenesis. Taken together, these results strongly suggest that MSCs play both responder and initiator roles in mediating the osteolytic effects of the presence of wear debris particles in periprosthetic zones.
authors.affiliation: Cartilage Biology and Orthopaedics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Department of Health and Human Service, Bethesda, Maryland 20892, USA.
authors.forename: Hana
authors.initials: H
authors.lastname: Haleem-Smith
authors.forename: Evan
authors.initials: E
authors.lastname: Argintar
authors.forename: Curtis
authors.initials: C
authors.lastname: Bush
authors.forename: Daniel
authors.initials: D
authors.lastname: Hampton
authors.forename: William F
authors.initials: WF
authors.lastname: Postma
authors.forename: Faye H
authors.initials: FH
authors.lastname: Chen
authors.forename: Todd
authors.initials: T
authors.lastname: Rimington
authors.forename: Joshua
authors.initials: J
authors.lastname: Lamb
authors.forename: Rocky S
authors.initials: RS
authors.lastname: Tuan
mesh_terms: D022005:Adherens Junctions / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004705:Endocytosis / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism / Q000494:pharmacology; D016209:Interleukin-8 / Q000378:metabolism / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects* / Q000235:genetics; D010014:Osteolysis / Q000139:chemically induced*; D052638:Particulate Matter / Q000009:adverse effects*; D014025:Titanium / Q000009:adverse effects*
chemical_list: D017077:Culture Media, Conditioned; D015850:Interleukin-6; D016209:Interleukin-8; D052638:Particulate Matter; D014025:Titanium
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