The Effects of Particulate Wear Debris, Cytokines, and Growth Factors on the Functions of MG-63 Osteoblasts

Vermes, Csaba; Chandrasekaran, Raman; Jacobs, Joshua J.; Galante, Jorge O.; Roebuck, Kenneth A.; Glant, Tibor T.

doi:10.2106/00004623-200102000-00007

Cited by 208 publications

(194 citation statements)

References 39 publications

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“…Finally, our findings also suggest independent mechanisms of macrophage activation since LPS stimulated IKBU catabolism, while titanium particles had minimal, if any activation. Thus, the particles used in these studies are a valuable method of to assess inflammatory effects in vitro and in vivo and are and well-accepted model commonly used by us and others [5,13,25,37,44,45].…”

Section: Discussionmentioning

confidence: 99%

The role of p105 protein in NFκB activation in ANA‐1 murine macrophages following stimulation with titanium particles

Soloviev

Schwarz

Kuprash

et al. 2002

Journal Orthopaedic Research

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Macrophage activation by particulate debris from orthopaedic implants triggers an inflammatory response that ultimately leads to periprosthetic bone resorption and implant failure. TNFa has been identified as a critical cytokine involved in the response to debris particles but the mechanisms involved in activation of TNFx synthesis are unclear. The current study demonstrates rapid induction of T N F r following stimulation with titanium particles in the murine macrophage cell line, ANA-1, Electrophoretic mobility shift assays demonstrated NFtiB DNA binding activity within 15 min of exposure to titanium particles, and experiments with an N FtiB luciferase promoter confirmed the induction of NFKB mediated transcription by titanium particles. Furthermore, titanium particles induced a ?-fold induction in T N F a promoter activity, and mutation of the tiB2a site, one of the four NFtiBbinding sites in the TNFx promoter, resulted in decreased activation. Since NFtiB is a critical regulator of inflammation and is involved in activation of the TNF? promoter, additional experiments were performed to determine the mechanism of N FtiB activation by particles. NFKB activation was found to be dependent upon proteasome activity, since administration of MG 132, a proteasome inhibitor, blocked NFtiB activation. However, ItiBa is only slightly decreased following Ti treatment, in contrast to marked degradation following stimulation with LPS. Recently, another proteasome-dependent pathway of NFtiB activation has been described involving degradation of p105, a precursor of p50 that binds to p65. p105 degradation occurred following titanium stimulation. suggesting that this recently described mechanism for NFtiB activation is operant in ANA-1 cells following exposure to titanium particles. These findings demonstrate that activation of the NFtiB signaling pathway is rapidly induced by titanium particles in ANA-1 cells and is associated with p105 degradation. TNF'r induction appears to be mediated, at least in part, through NFtiB binding to the ~B 3 a site of the TNFx promoter. 8

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Section: Discussionmentioning

confidence: 99%

The role of p105 protein in NFκB activation in ANA‐1 murine macrophages following stimulation with titanium particles

Soloviev

Schwarz

Kuprash

et al. 2002

Journal Orthopaedic Research

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“…Other cells of potential interest in the pathology of debris-induced osteolysis include osteoclasts [28,58,60], osteoblasts [71], lymphocytes [7], and mesenchymal cells [62].…”

Section: Search Strategy and Criteriamentioning

confidence: 99%

How Has the Introduction of New Bearing Surfaces Altered the Biological Reactions to Byproducts of Wear and Modularity?

Wooley

2014

Clin Orthop Relat Res

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Background Biological responses to wear debris were largely elucidated in studies focused on conventional ultrahigh-molecular-weight polyethylene (UHMWPE) and some investigations of polymethymethacrylate cement and orthopaedic metals. However, newer bearing couples, in particular metal-on-metal but also ceramic-on-ceramic bearings, may induce different biological reactions. Questions/purposes Does wear debris from the newer bearing surfaces result in different biological responses compared with the known responses observed with conventional metal-on-UHMWPE bearings?Methods A Medline search of articles published after 1996 supplemented by a hand search of reference lists of included studies and relevant conference proceedings was conducted to identify the biological responses to orthopaedic wear debris with a focus on biological responses to wear generated from metal-on-highly crosslinked polyethylene, metal-on-metal, ceramic-on-ceramic, and ceramicon-polyethylene bearings. Articles were selected using criteria designed to identify reports of wear debris particles and biological responses contributing to prosthesis failure. Case reports and articles focused on either clinical outcomes or tribology were excluded. A total of 83 papers met the criteria and were reviewed in detail.

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“…It is therefore important to consider whether, in addition to promoting osteoclast activity, wear debris might also contribute to osteolysis by inhibiting bone formation. Wear debris particles have been shown to decrease expression of collagen types I and III by osteoblasts (OBs), the cell type responsible for bone formation [76][77][78]. In addition, titanium has been reported to reduce OB viability by inducing apoptosis [79], and PMMA bone cement reduces OB proliferation [80].…”

Section: Bone Formation Cellsmentioning

confidence: 99%

The Central Role of Wear Debris in Periprosthetic Osteolysis

Purdue

Koulouvaris

Nestor

et al. 2006

HSS Journal®: The Musculoskeletal Journal of Hospital for Speci

217

190

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Periprosthetic osteolysis remains the leading complication of total hip arthroplasty, often resulting in aseptic loosening of the implant, and a requirement for revision surgery. Wear-generated particular debris is the main cause of initiating this destructive process. The purpose of this article is to review recent advances in our understanding of how wear debris causes osteolysis, and emergent strategies for the avoidance and treatment of this disease. The most important cellular target for wear debris is the macrophage, which responds to particle challenge in two distinct ways, both of which contribute to increased bone resorption. First, it is well known that wear debris activates proinflammatory signaling, which leads to increased osteoclast recruitment and activation. More recently, it has been established that wear also inhibits the protective actions of antiosteoclastogenic cytokines such as interferon gamma, thus promoting differentiation of macrophages to bone-resorbing osteoclasts. Osteoblasts, fibroblasts, and possibly lymphocytes may also be involved in responses to wear. At a molecular level, wear particles activate MAP kinase cascades, NF.B and other transcription factors, and induce expression of suppressors of cytokine signaling. Strategies to reduce osteolysis by choosing bearing surface materials with reduced wear properties (such as metal-on-metal) should be balanced by awareness that reducing particle size may increase biological activity. Finally, although therapeutic agents against proinflammatory mediators [such as tumor necrosis factor (TNF)] and osteoclasts (bisphosphonates and molecules blocking RANKL signaling) have shown promise in animal models, no approved treatments are yet available to osteolysis patients. Considerable efforts are underway to develop such therapies, and to identify novel targets for therapeutic intervention.

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The Effects of Particulate Wear Debris, Cytokines, and Growth Factors on the Functions of MG-63 Osteoblasts

Cited by 208 publications

References 39 publications

The role of p105 protein in NFκB activation in ANA‐1 murine macrophages following stimulation with titanium particles

The role of p105 protein in NFκB activation in ANA‐1 murine macrophages following stimulation with titanium particles

How Has the Introduction of New Bearing Surfaces Altered the Biological Reactions to Byproducts of Wear and Modularity?

The Central Role of Wear Debris in Periprosthetic Osteolysis

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