Foreign body giant cells and osteoclasts are TRAP positive, have podosome‐belts and both require OC‐STAMP for cell fusion

Khan, Usman; Hashimi, Saeed Mujahid; Bakr, Mahmoud M.; Forwood, Mark R.; Morrison, Nigel Alexander

doi:10.1002/jcb.24518

Cited by 51 publications

(41 citation statements)

References 30 publications

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“…OC-STAMP was also demonstrated to be required for FBGC cell–cell fusion 14 . Recently, OC-STAMP antibody was demonstrated to inhibit osteoclast and FBGC cell–cell fusion 37 . Thus, DC-STAMP and OC-STAMP were both required for osteoclast and FBGC cell–cell fusion.…”

Section: Identification Of Oc-stampmentioning

confidence: 99%

STATs and macrophage fusion

Miyamoto¹

2013

JAK-STAT

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Macrophages play a pivotal role in host defense against multiple foreign materials such as bacteria, parasites and artificial devices. Some macrophage lineage cells, namely osteoclasts and foreign body giant cells (FBGCs), form multi-nuclear giant cells by the cell–cell fusion of mono-nuclear cells. Osteoclasts are bone-resorbing cells, and are formed in the presence of RANKL on the surface of bones, while FBGCs are formed in the presence of IL-4 or IL-13 on foreign materials such as artificial joints, catheters and parasites. Recently, fusiogenic mechanisms and the molecules required for the cell–cell fusion of these macrophage lineage cells were, at least in part, clarified. Dendritic cell specific transmembrane protein (DC-STAMP) and osteoclast stimulatory transmembrane protein (OC-STAMP), both of which comprise seven transmembrane domains, are required for both osteoclast and FBGC cell–cell fusion. STAT6 was demonstrated to be required for the cell–cell fusion of FBGCs but not osteoclasts. In this review, advances in macrophage cell–cell fusion are discussed.

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Section: Identification Of Oc-stampmentioning

confidence: 99%

STATs and macrophage fusion

Miyamoto¹

2013

JAK-STAT

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“…In contrast, other results indicate that material‐induced MNGCs are involved in the inflammatory reaction cascade called “foreign body reaction to biomaterials” and, thus, MNGCs have been attributed to the foreign body giant cell (FBGC) type . Although it has been shown that some similarities exist between osteoclasts and biomaterial‐adherent MNGCs, it has been shown that the latter cell type did not exhibit essential characteristics of osteoclasts, such as a ruffled cell border and the induction of other molecules such as interleukin‐4 and −13 (IL‐4/‐13).…”

Section: Introductionmentioning

confidence: 99%

Multinucleated giant cells in the implant bed of bone substitutes are foreign body giant cells—New insights into the material‐mediated healing process

Barbeck

Booms

Unger

et al. 2017

J Biomedical Materials Res

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In addition to macrophages, multinucleated giant cells (MNGCs) are involved in the tissue reaction to a variety of biomaterials. Especially in the case of bone substitute materials it has been assumed that the MNGCs are osteoclasts, based on the chemical and physical similarity of many materials to the calcified matrix and the bony environment in which they are used. However, many studies indicate that these cells belong to the cell line of the foreign body giant cells (FBGCs), which are of "inflammatory origin", although they have been shown to possess both a pro- and also anti-inflammatory phenotype. Moreover, no information is available about their role in the tissue reaction to bone substitute materials. The present study was conducted to analyze the origin of MNGCs in the implant beds of a synthetic and a xenogeneic bone substitute and focused on the application of immunohistochemical methods. Two antibodies against integrin molecules specific for osteoclasts (β-3 integrin) or FBGCs (β-2 integrin) were used to distinguish both giant cell types. The results of the present study indicate that the MNGCs induced by both kinds of bone substitutes are FBGCs, as they express only β-2 integrin in contrast to the osteoclasts outside of the immediate implantation areas, which only demonstrate β-3 integrin expression. These data give new insight into the tissue reaction to both xenogeneic and synthetic bone substitutes. Based on this new knowledge further research concerning the proteomic profile of the FBGCs especially based on the different physicochemical properties of bone substitutes is necessary. This may show that specific characteristics of bone substitutes may exhibit a substantial influence on the regeneration process via the expression of anti-inflammatory molecules by FBGCs. Based on this information it may be possible to formulate and choose bone substitutes that can guide the process of bone tissue regeneration on the molecular level. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1105-1111, 2017.

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“…RAW 264.7 represents a well‐established, reproducible and easy to maintain pre‐osteoclastic cell line, also recommended by the American Society of Testing and Materials for the biocompatibility studies of new medical devices materials . However, although osteoclasts share origin, characteristics and functions overlapping with macrophages and foreign body giant cells, we chose to distinguish univocally osteoclasts, morphologically by F‐actin ring staining, functionally by pit formation assay on dentine disks and at molecular level by measuring the key transcription factor of osteoclastogenesis (NFATc1) and early and late osteoclast specific markers (RANK, OSCAR, RANKL) . Nonetheless, caution should be used in extrapolating results obtained with RAW 264.7 cells due to permanent alterations in their genes leading to cells that grow continuously, are easily activated and over‐express molecules in a quite different manner from primary macrophages.…”

Section: Discussionmentioning

confidence: 99%

RAW 264.7 co‐cultured with ultra‐high molecular weight polyethylene particles spontaneously differentiate into osteoclasts: an in vitro model of periprosthetic osteolysis

Sartori

Vincenzi

Ravani

et al. 2016

J Biomedical Materials Res

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Wear-particle osteolysis affects prosthesis survival leading to implant loosening up to 70% of revisions. Therapeutic strategies are increasing, however alternative testing methods to experimentally evaluate such treatments are lacking. The aim of this study was to reproduce an in vitro osteolysis model recapitulating the events that, starting from the exposure of macrophages to polyethylene, lead to the establishment of osteoclastogenesis and inflammation. Responses to polyethylene, at 3 and 7 days, in a macrophage cell line, RAW 264.7, were determined by DNA quantification, immunofluorescence, pit assay, gene expression, cytokine production and NF-kB activation. Results showed that 3 days exposure to particles could induce a significant production of Tumor Necrosis Factor alpha (p < 0.0005) and Prostaglandin E (p < 0.005) compared to controls. Particles also induced macrophages to spontaneously differentiate into mature and active osteoclasts, in terms of identification of multinucleated cells by Phalloidin staining and by the analysis of osteoclast-specific gene markers. In particular, at 3 days polyethylene induced a significant up-regulation of Nuclear Factor of Activated T-cells, cytoplasmic 1, Receptor Activator of Nuclear factor Kappa-B and Receptor Activator of Nuclear Factor Kappa-B Ligand genes (p < 0.0005) compared to controls. At protein level, the particles induced a significant increase of Receptor Activator of Nuclear Factor Kappa-B Ligand at day 7 over controls (p < 0.0005). Osteoclasts were capable to resorb bone even in absence of differentiating factors. The possible mechanism, beside spontaneous osteoclastogenesis mediated by wear debris, was identified in an autocrine up-regulation of Receptor activator of nuclear factor kappa-B ligand gene expression and protein synthesis. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 510-520, 2017.

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Foreign body giant cells and osteoclasts are TRAP positive, have podosome‐belts and both require OC‐STAMP for cell fusion

Cited by 51 publications

References 30 publications

STATs and macrophage fusion

STATs and macrophage fusion

Multinucleated giant cells in the implant bed of bone substitutes are foreign body giant cells—New insights into the material‐mediated healing process

RAW 264.7 co‐cultured with ultra‐high molecular weight polyethylene particles spontaneously differentiate into osteoclasts: an in vitro model of periprosthetic osteolysis

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