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Biological responses of human mesenchymal stem cells to titanium wear debris particles
Author(s) -
HaleemSmith Hana,
Argintar Evan,
Bush Curtis,
Hampton Daniel,
Postma William F.,
Chen Faye H.,
Rimington Todd,
Lamb Joshua,
Tuan Rocky S.
Publication year - 2012
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.22002
Subject(s) - mesenchymal stem cell , viability assay , microbiology and biotechnology , osteolysis , cell , stem cell , chemistry , medicine , biology , surgery , biochemistry
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. © 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:853–863, 2012