The Impact of Metal Ion Exposure on the Cellular Behavior of Human Osteoblasts and PBMCs: In Vitro Analyses of Osteolytic Processes

Jonitz‐Heincke, Anika; Tillmann, Jenny; Klinder, Annett; Krueger, Simone; Kretzer, Jan Philippe; Høl, Paul Johan; Paulus, Alexander; Bader, Rainer

doi:10.3390/ma10070734

Cited by 19 publications

(25 citation statements)

References 31 publications

(49 reference statements)

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“…Exposure to wear debris induces the expression of pro‐inflammatory cytokines and other inflammatory mediators, which are involved in adverse local tissue reaction and periprosthetic osteolysis . Moreover, cytotoxic effects and altered gene expression levels for the components of CoCrMo have been reported in chondrocytes and various other cell types …”

Section: Discussionmentioning

confidence: 99%

Effects of Loading Conditions on Articular Cartilage in a Metal‐on‐Cartilage Pairing

Stotter

Stojanović

Bauer

et al. 2019

Journal Orthopaedic Research

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The aim of this in vitro study was to investigate the response of articular cartilage to frictional load when sliding against a metal implant, and identify potential mechanisms of damage to articular cartilage in a metal-on-cartilage pairing. Bovine osteochondral cylinders were reciprocally slid against metal cylinders (cobalt-chromium-molybdenum alloy) with several variations of load and sliding velocity using a microtribometer. The effects of different loads and velocities, and the resulting friction coefficients on articular cartilage, were evaluated by measuring histological and metabolic outcomes. Moreover, the biotribocorrosion of the metal was determined. Chondrocytes stimulated with high load and velocity showed increased metabolic activity and cartilage-specific gene expression. In addition, higher load and velocity resulted in biotribocorrosion of the metal implant and damage to the surface of the articular cartilage, whereas low velocity and a high coefficient of friction increased the expression of catabolic genes. Articular cartilage showed particular responses to load and velocity when sliding against a metal implant. Moreover, metal implants showed tribocorrosion. Therefore, corrosion particles may play a role in the mechano-biochemical wear of articular cartilage after implantation of a metal implant. These findings may be useful to surgeons performing resurfacing procedures and total knee arthroplasty.

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Section: Discussionmentioning

confidence: 99%

Effects of Loading Conditions on Articular Cartilage in a Metal‐on‐Cartilage Pairing

Stotter

Stojanović

Bauer

et al. 2019

Journal Orthopaedic Research

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“…AZ: A2011-140). Isolation of PBMCs was done by density gradient centrifugation at 320 × g and 230 × g with Histopaque ® -1077 (Sigma Aldrich) accordingly to the protocol described in previous work ( 37 ). Cells were cultivated in Roswell Park Memorial Institute (RPMI) 1640 medium (Biochrom AG) supplemented with 5% FCS (Gibco ® Invitrogen), 1% penicillin/streptomycin, and 1% l -glutamine (both: Sigma-Aldrich) at 37°C and 5% CO 2 .…”

Section: Methodsmentioning

confidence: 99%

Inflammatory Response of Human Peripheral Blood Mononuclear Cells and Osteoblasts Incubated With Metallic and Ceramic Submicron Particles

et al. 2018

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Inflammatory reactions associated with osteolysis and aseptic loosening are the result of wear particles generated at the articulating surfaces of implant components. The aim of the present study was to analyze the biological response of human osteoblasts and peripheral blood mononuclear cells (PBMCs) after exposure to metallic and alumina ceramic particles regarding cellular differentiation, cytokine release, and monocyte migration. Cells were exposed to particles (0.01 and 0.05 mg/ml) from an alumina matrix composite (AMC) ceramic and a CoCr28Mo6 alloy with an average size of 0.5 µm over 48 and 96 h. The expression rates of osteogenic (Col1A1, ALP) and pro-osteoclastic (RANK, Trap5b) differentiation markers as well as pro-osteolytic mediators (MMP-1, TIMP-1, IL-6, IL-8, MCP-1) were determined and soluble protein concentrations of active MMP-1, IL-6, IL-8, and pro-collagen type 1 in cell culture supernatants were evaluated. Additionally, the capacity of particle-treated osteoblasts to attract potentially pro-inflammatory cells to the site of particle exposure was investigated by migration assays using osteoblast-conditioned media. The cellular morphology and metabolism of human osteoblasts and adherent PBMCs were influenced by particle type and concentration. In human osteoblasts, Col1A1 expression rates and protein production were significantly reduced after exposing cells to the lower concentration of cobalt-chromium (CoCr) and AMC particles. Exposure to AMC particles (0.01 mg/ml) resulted in increased mRNA levels of RANK and Trap5b in adherent PBMCs. For MMP-1 gene expression, elevated levels were more prominent after incubation with CoCr compared to AMC particles in osteoblasts, which was not reflected by the protein data. Interleukin (IL)-6 and IL-8 mRNA and protein were induced in both cell types after treatment with AMC particles, whereas exposure to CoCr particles resulted in significantly upregulated IL-6 and IL-8 protein contents in PBMCs only. Exposure of osteoblasts to CoCr particles reduced the chemoattractant potential of osteoblast-conditioned medium. Our results demonstrate distinct effects of AMC and CoCr particles in human osteoblasts and PBMCs. Complex cell and animal models are required to further evaluate the impact of cellular interactions between different cell types during particle exposure.

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“…In light of the limitations mentioned above, an established murine model was used in this study, which mimics the initial biological reactions in the synovial-like tissues around prostheses caused by metal particles and ions [35,[37][38][39]. In contrast to various in vitro cell culture studies that focus on one cell type [32,40], the murine model can not only reflect complex cellular and tissue interactions, but can also mimic the dynamic process of joints. Additionally, compared with other models, such as hamsters' skinfold-chamber models [41] and "air pouch" models [42], results from this model, as the suspensions were injected intraarticularly, are easier to translate into a clinical scenario because the generated wear debris primarily accumulates in the joint that has been replaced.…”

Section: Discussionmentioning

confidence: 99%

“…Using HR-ICP-MS, a total metal ion content (cobalt, chromium, nickel and molybdenum) of 20.5 mg/L was determined, which was adjusted to the desired target concentration of 200 µg/L using PBS (Table 2) [32]. The target concentration of ions was based on the concentration measured in the synovial fluid of patients with endoprosthesis during revision surgery [22].…”

Section: Ecd Aspect Ratio Roundnessmentioning

confidence: 99%

Biological Reactions to Metal Particles and Ions in the Synovial Layer of Mice

et al. 2020

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Metal particles and ions released from implants not only have a fundamental effect on the longevity of total joint replacements, but can also be disseminated to remote organs. Periprosthetic tissues harvested during revision surgeries mainly reflect end-stage failure but may not adequately reveal initial biological reactions and systemic side effects. Therefore, primary reactions caused by metal particles and ions were investigated in an established murine model. Left knee joints in three groups, each consisting of ten female BALB/c mice, received injections of metal ions (MI), metal particles (MP) and phosphate-buffered saline (PBS) (control). Seven days after the injection, immunohistochemical analyses of the synovial layer were performed with respect to some biological markers including Tumor necrosis factor -α (TNF-α), Interleukin-6 (IL-6), Interleukin-1β (IL-1β), Cluster of Differentiation 45 (CD45), Cluster of Differentiation 68 (CD68) and Cluster of Differentiation 3(CD3). The MP group showed significantly enhanced proinflammatory cytokine expression (TNF-α, IL-6 and IL-1β) compared with the other groups (p < 0.05). Interestingly, CD3, as a marker for T lymphocytes, did not increase in any of the groups. The MI group showed a significantly increased expression of CD45 compared with the control group (p < 0.05). Therefore, during the primary process, metal particles have stronger pro-inflammatory potential than metal ions, and T lymphocytes did not seem to be activated in our murine model. Systemic reactions caused by metal particles and ions were found by observing the untreated right knees.

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The Impact of Metal Ion Exposure on the Cellular Behavior of Human Osteoblasts and PBMCs: In Vitro Analyses of Osteolytic Processes

Cited by 19 publications

References 31 publications

Effects of Loading Conditions on Articular Cartilage in a Metal‐on‐Cartilage Pairing

Effects of Loading Conditions on Articular Cartilage in a Metal‐on‐Cartilage Pairing

Inflammatory Response of Human Peripheral Blood Mononuclear Cells and Osteoblasts Incubated With Metallic and Ceramic Submicron Particles

Biological Reactions to Metal Particles and Ions in the Synovial Layer of Mice

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