Gene expression in adverse reaction to metal debris around metal-on-metal arthroplasty: An RNA-Seq-based study

Pemmari, Antti; Leppänen, Tiina; Paukkeri, Erja-Leena; Eskelinen, Antti; Moilanen, Teemu; Moilanen, Eeva

doi:10.1016/j.jtemb.2018.03.014

Cited by 6 publications

(5 citation statements)

References 61 publications

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“…The cytotoxic response to CoCr wear particles was in agreement with the previous studies 22 . Moreover, genetic variability within the genes encoding inflammation and hypoxia-related biochemical mediators could be the reason behind the variable cytotoxic responses to CoCr wear debris observed in this study 46 , 47 . Extensive but variable necrosis has also been reported as a distinguishing feature of adverse reactions to metal debris (ARMD) in tissues from failed metal on metal implants 48 .…”

Section: Discussionmentioning

confidence: 86%

Biological Impact of Silicon Nitride for Orthopaedic Applications: Role of Particle Size, Surface Composition and Donor Variation

Lal

Caseley

Hall

et al. 2018

Sci Rep

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The adverse biological impact of orthopaedic wear debris currently limits the long-term safety of human joint replacement devices. We investigated the role of particle size, surface composition and donor variation in influencing the biological impact of silicon nitride as a bioceramic for orthopaedic applications. Silicon nitride particles were compared to the other commonly used orthopaedic biomaterials (e.g. cobalt-chromium and Ti-6Al-4V alloys). A novel biological evaluation platform was developed to simultaneously evaluate cytotoxicity, inflammatory cytokine release, oxidative stress, and genotoxicity potential of particles using peripheral blood mononuclear cells (PBMNCs) from individual human donors. Irrespective of the particle size, silicon nitride did not cause any adverse responses whereas cobalt-chromium wear particles caused donor-dependent cytotoxicity, TNF-α cytokine release, oxidative stress, and DNA damage in PBMNCs after 24 h. Despite being similar in size and morphology, silicon dioxide nanoparticles caused the release of significantly higher levels of TNF-α compared to silicon nitride nanoparticles, suggesting that surface composition influences the inflammatory response in PBMNCs. Ti-6Al-4V wear particles also released significantly elevated levels of TNF-α cytokine in one of the donors. This study demonstrated that silicon nitride is an attractive orthopaedic biomaterial due to its minimal biological impact on human PBMNCs.

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Section: Discussionmentioning

confidence: 86%

Biological Impact of Silicon Nitride for Orthopaedic Applications: Role of Particle Size, Surface Composition and Donor Variation

Lal

Caseley

Hall

et al. 2018

Sci Rep

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“…CD52 is widely present on most human lymphocytes and expresses on the cell membrane via a glycosylphosphatidylinositol (GPI) anchor (Pemmari et al, 2018). Although little is known about its exact physiological function, CD52 has shown to be a promising target for several immune system-mediated diseases, such as multiple sclerosis (MS), autoimmune inflammatory neurodegenerative diseases, allergic asthma, and lymphocytic leukemia (Shafiei-Jahani et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Identification of susceptibility modules and hub genes of osteoarthritis by WGCNA analysis

et al. 2022

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Osteoarthritis (OA) is a major cause of pain, disability, and social burden in the elderly throughout the world. Although many studies focused on the molecular mechanism of OA, its etiology remains unclear. Therefore, more biomarkers need to be explored to help early diagnosis, clinical outcome measurement, and new therapeutic target development. Our study aimed to retrieve the potential hub genes of osteoarthritis (OA) by weighted gene co-expression network analysis (WGCNA) and assess their clinical utility for predicting OA. Here, we integrated WGCNA to identify novel OA susceptibility modules and hub genes. In this study, we first selected 477 and 834 DEGs in the GSE1919 and the GSE55235 databases, respectively, from the Gene Expression Omnibus (GEO) website. Genes with p-value<0.05 and | log2FC | > 1 were included in our analysis. Then, WGCNA was conducted to build a gene co-expression network, which filtered out the most relevant modules and screened out 23 overlapping WGCNA-derived hub genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses elucidated that these hub genes were associated with cell adhesion molecules pathway, leukocyte activation, and inflammatory response. In addition, we conducted the protein–protein interaction (PPI) network in 23 hub genes, and the top four upregulated hub genes were sorted out (CD4, SELL, ITGB2, and CD52). Moreover, our nomogram model showed good performance in predicting the risk of OA (C-index = 0.76), and this model proved to be efficient in diagnosis by ROC curves (AUC = 0.789). After that, a single-sample gene set enrichment (ssGSEA) analysis was performed to discover immune cell infiltration in OA. Finally, human primary synoviocytes and immunohistochemistry study of synovial tissues confirmed that those candidate genes were significantly upregulated in the OA groups compared with normal groups. We successfully constructed a co-expression network based on WGCNA and found out that OA-associated susceptibility modules and hub genes, which may provide further insight into the development of pre-symptomatic diagnosis, may contribute to understanding the molecular mechanism study of OA risk genes.

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“…Enrichment analyses revealed the oxidative stress pathway was significantly upregulated (Supplementary Figure S1e3), and its expression is considered an indicator of macrophage oxidative stress induced by metal/metal oxide nanomaterials [33]. Increased levels of Hmox1 have been found in patients with CoCr prosthetic implants [34]. Heme oxygenase 1 (Hmox1) is a well-known antioxidant stress protein whose expression is induced by various stressors such as oxidative stress and heavy metals [35] and its expression is considered a reporter of macrophage oxidative stress induced by metal/metal oxide nanomaterials [33].…”

Section: Cocr Surfacesmentioning

confidence: 99%

“…All of this suggests that higher levels of Hmox1 could also be a way to protect against oxidative stress caused by CoCr tribocorrosion. In fact, increased mRNA levels of Hmox1 have been found in pseudosynovial tissue removed from CoCr hip arthroplasties that developed adverse reactions to metal debris [34].…”

Section: Cocr Surfacesmentioning

confidence: 99%

Effect of Wear-Corrosion of Reduced Graphene Oxide Functionalized with Hyaluronic Acid on Inflammatory and Proteomic Response of J774A.1 Macrophages

Sánchez-López

Torres

Chico

et al. 2023

Metals

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The presence of a worn surface in the implanted material, as in the case of a replacement of a damaged osteoarticular joint, is the normal condition after implantation. This manuscript focuses precisely on the comparative study of the cellular behavior on worn CoCr surfaces, analyzing the effect of different surface modifications on macrophages’ responses. CoCr surfaces were modified by the deposition of electrochemically reduced graphene oxide (CoCrErGO), followed by additional surface functionalization with hyaluronic acid (CoCrErGOHA). After the wear corrosion processes, the macrophage response was studied. In addition, macrophage supernatants exposed to the surfaces, before and after wear, were also evaluated for osteoblast response through the analysis of the metabolic activity, plasma membrane damage, and phosphatase alkaline activity (ALP). The proteomic analysis and the quantitative TNF-α/IL-10 ratios of the J774A.1 macrophages exposed to the surfaces under study showed a polarization shift from M0 (basal state) to M1, associated with the pro-inflammatory response of all surfaces. A lower M1 polarization was observed upon exposure to the surface modification with ErGO, whereas posterior HA functionalization attenuated, even more, the M1 polarization. The wear corrosion process contributed to inflammation and exacerbated the M1 polarization response on macrophages to CoCr, which was diminished for the ErGO and attenuated the most for the ErGOHA surfaces. Comparative proteomics showed that the pathways related to M1 polarization were downregulated on the surfaces of CoCrErGOHA, which suggests mechanisms for the observed attenuation of M1 polarization. The suitable immuno-modulatory potential induced by the ErGOHA surface, with and without wear, together with the stimulation of ALP activity in osteoblasts induced by macrophage supernatants, promotes the mineralization processes necessary for bone repair. This makes it feasible to consider the adsorption of ErGOHA on CoCr as a recommended surface treatment for the use of biomaterials in osseous joint applications.

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Gene expression in adverse reaction to metal debris around metal-on-metal arthroplasty: An RNA-Seq-based study

Cited by 6 publications

References 61 publications

Biological Impact of Silicon Nitride for Orthopaedic Applications: Role of Particle Size, Surface Composition and Donor Variation

Biological Impact of Silicon Nitride for Orthopaedic Applications: Role of Particle Size, Surface Composition and Donor Variation

Identification of susceptibility modules and hub genes of osteoarthritis by WGCNA analysis

Effect of Wear-Corrosion of Reduced Graphene Oxide Functionalized with Hyaluronic Acid on Inflammatory and Proteomic Response of J774A.1 Macrophages

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