Adherent Endotoxin on Orthopedic Wear Particles Stimulates Cytokine Production and Osteoclast Differentiation
Abstract
Aseptic loosening of orthopedic implants is thought to be caused primarily by osteoclast differentiation induced by bone resorptive cytokines produced in response to phagocytosis of implant-derived wear particles. This study examined whether adherent endotoxin on the wear particles is responsible for inducing osteoclast differentiation as well as production of interleukin-1beta (IL-1beta), IL-6, and tumor necrosis factor a (TNF-alpha). Removal of adherent endotoxin almost completely inhibited the responses to titanium (Ti) particles by both murine marrow cells and human peripheral blood monocytes. In vivo experiments showed that endotoxin removal reduced particle-induced osteolysis by 50-70%. Addition of lipopolysaccharide (LPS) to the "endotoxin-free" particles restored their ability to induce cytokine production and osteoclast differentiation in vitro. Moreover, marrow cells from mice that are hyporesponsive to endotoxin because of mutation of Toll-like receptor 4 induced significantly less cytokine production and osteoclast differentiation in response to Ti particles with adherent endotoxin than did marrow cells from normoresponsive mice. This mutation also resulted in significantly less particle-induced osteolysis in vivo. Taken together, these results show that adherent endotoxin is involved in many of the biological responses induced by orthopedic wear particles and should stimulate development of new approaches designed to reduce the activity of adherent endotoxin in p…
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Removal of adherent endotoxin on orthopedic wear particles almost completely eliminated IL-1β, IL-6, and TNF-α production from human monocytes.
“Removal of adherent endotoxin on orthopedic wear particles almost completely eliminated IL-1β, IL-6, and TNF-α production from human monocytes.[128]”
From Foreign body reaction to biomaterials (2008) · cites this paper as [128]
Contamination with endotoxin and other bacterial byproducts may occur during implant lifetime, leading to further pro-inflammatory activation and adverse outcomes.
“Additionally, contamination with endotoxin and other bacterial byproducts may occur during the lifetime of the implant, leading to further pro-inflammatory activation and adverse outcomes [146].”
From Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine (2012) · cites this paper as [146]
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Foreign body reaction to biomaterials
Anderson, J. M., Rodriguez, A., & Chang, D. T. (2008) · Seminars in Immunology · doi:10.1016/j.smim.2007.11.004 · Cited by 5,138 · see citing works
Self-citationBrown, B. N., Ratner, B. D., Goodman, S. B., Amar, S., & Badylak, S. F. (2012) · Biomaterials · doi:10.1016/j.biomaterials.2012.02.034 · Cited by 926 · see citing works
Integrin-directed modulation of macrophage responses to biomaterials
Zaveri, T. D., Lewis, J. S., Dolgova, N. V., Clare-Salzler, M. J., & Keselowsky, B. G. (2014) · Biomaterials · doi:10.1016/j.biomaterials.2014.01.007 · Cited by 164 · see citing works
- Authors
- Bi, Y., Seabold, J. M., Kaar, S. G., Ragab, A. A., Goldberg, V. M., Anderson, J. M., & Greenfield, E. M.
- Affiliations
- Case Western Reserve University (US)
- Corresponding author
- Greenfield, Edward M.
- Venue
- Journal of Bone and Mineral Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2001-11-01
- Volume
- 16
- Issue
- 11
- Pages
- 2082-2091
- ISSN
- 0884-0431 (ISSN-L)
- 1523-4681
- OpenAlex
- W2078844869
- Cited by
- 227
- References
- 1
- Citations by year
- 2025: 3 · 2024: 3 · 2023: 4 · 2022: 6 · 2021: 7 · 2020: 10 · 2019: 10 · 2018: 13 · 2017: 7 · 2016: 12 · 2015: 8 · 2014: 17 · 2013: 15 · 2012: 13
- FWCI
- 7.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Journal of Bone and Mineral Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL 33849)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR-07505, AR43769, T32AR007505, R01AR043769)
- Topics
- Health Sciences › Medicine › Surgery › Orthopaedic implants and arthroplasty
- Health Sciences › Medicine › Surgery › Orthopedic Infections and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Keywords
- endotoxin, aseptic loosening, osteoclastogenesis, cytokine production, titanium particles, lipopolysaccharide, osteolysis, TLR4, bone resorption, monocytes, bone marrow cells
- MeSH terms
- Adhesiveness, Animals, Bone Resorption, Cell Differentiation, Endotoxins, Humans, Lipopolysaccharides, Membrane Glycoproteins, Mice, Inbred BALB C, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, Mutant Strains, Monocytes, Mutation, Osteoclasts, Osteolysis, Prosthesis Failure, Receptors, Cell Surface, Cytokines, Drosophila Proteins, Toll-Like Receptors, Toll-Like Receptor 4, Mice, In Vitro Techniques
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