ArticleJournal of cellular physiology2008
Stimulation of macrophage TNFalpha production by orthopaedic wear particles requires activation of the ERK1/2/Egr-1 and NF-kappaB pathways but is independent of p38 and JNK.
Article in Journal of cellular physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 31 citations in OpenAlex.
- The dual role of titanium particles in osteolysis: implications for gene therapy in prosthesis loosening.European journal of medical research · 2025Article
- BMP-2 functional polypeptides relieve osteolysis via bi-regulating bone formation and resorption coupled with macrophage polarization.NPJ Regenerative medicine · 2023Article
- Lysosomal disruption by orthopedic wear particles induces activation of the NLRP3 inflammasome and macrophage cell death by distinct mechanisms.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2021Article
- Effect of Aging on the Macrophage Response to Titanium Particles.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2020Article
- Successful and failed mini-implants: microbiological evaluation and quantification of bacterial endotoxin.Journal of applied oral science : revista FOB · 2018Article
- Mathematical model of chronic pancreatitis.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Activation of Egr-1 in human lung epithelial cells exposed to silica through MAPKs signaling pathways.PloS one · 2013Article
- PI3Kγ deletion reduces variability in the in vivo osteolytic response induced by orthopaedic wear particles.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2011Article
- Titanium particles activate toll-like receptor 4 independently of lipid rafts in RAW264.7 murine macrophages.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2011Article
- Hepatic response to oxidative injury in long-lived Ames dwarf mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2011Article
- Bacterial pathogen-associated molecular patterns stimulate biological activity of orthopaedic wear particles by activating cognate Toll-like receptors.The Journal of biological chemistry · 2010Article
- Deletion of caveolin-1 protects hyperoxia-induced apoptosis via survivin-mediated pathways.American journal of physiology. Lung cellular and molecular physiology · 2009Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Bone loss that causes aseptic loosening of orthopedic implants is initiated by pro-inflammatory cytokines produced by macrophages in response to implant-derived wear particles. MAPK and NF-kappaB signaling pathways are activated by the particles; however, it is not clear which of the signaling pathways are important for the initial response to the wear particles and which are only involved at later steps in the process, such as osteoclast differentiation. Here, we show that the ERK1/2, p38, JNK, and NF-kappaB pathways are rapidly activated by the wear particles but that only the ERK1/2 and NF-kappaB pathways are required for the initial response to the wear particles, which include increases in TNFalpha promoter activity, TNFalpha mRNA expression, and secretion of TNFalpha protein. Moreover, ERK1/2 activation by wear particles is also required for increased expression of the transcription factor Egr-1 as well as Egr-1's ability to bind to and activate the TNFalpha promoter. These results, together with our previous studies of the PI3K/Akt pathway, demonstrate that wear particles coordinately activate multiple signaling pathways and multiple transcription factors to stimulate production of pro-inflammatory cytokines, such as TNFalpha. The current study also demonstrates that the signaling pathways are activated to a much greater extent by wear particles with adherent endotoxin than by "endotoxin-free" wear particles. These results, together with those demonstrating the requirement for ERK1/2/Egr-1 and NF-kappaB, show that activation of these signaling pathways is responsible for the ability of adherent endotoxin to potentiate cytokine production, osteoclast differentiation, and bone loss induced by wear particles.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.