Size Dependent Enzyme Activities of Multinucleated (Osteoclastic) Giant Cells in Bone Tumors

Metze, Konradin; Ciplea, A.G.; Hettwer, H.; Barckhaus, R.H.

doi:10.1016/s0344-0338(87)80107-3

Cited by 10 publications

(4 citation statements)

References 35 publications

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“…Moreover, reduction in OPG by siRNA treatment did not affect the expression of OSCAR, an osteoclast differentiation marker gene (Merck et al ., 2004), Atp6vOd2 and DC-STAMP, fusion-related molecules (Yagi et al , 2005; Lee et al ., 2006), and αv and β3 integrin, adhesion molecules (Lacey et al , 1998; Nakamura et al ., 1999), but of note, it negatively affected the activity and expression of TRAP and cathepsin K, bone lytic enzymes (Lacey et al ., 1998; Boyle et al ., 2003). These results are consistent with the findings of a previous report, which suggested that large osteoclasts had low TRAP activities (Metze et al ., 1987). Regarding the cell size, it is certain that the increase in size was accomplished by multinucleation (Fig.…”

Section: Discussionsupporting

confidence: 94%

“…Bone-resorbing activity of mononuclear osteoclasts is lower than that of multinucleated osteoclasts (Yagi et al , 2005; Miyamoto, 2011; Chiu et al , 2012). In addition, TRAP activities in multinucleated osteoclastic giant cells of medium size are size-dependent, and the large cells reveal, in part, low activities (Metze et al , 1987). In this study, the size and bone-resorbing activity of osteoclasts induced by RANKL were increased throughout the differentiation processes.…”

Section: Discussionmentioning

confidence: 99%

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Osteoprotegerin Expressed by Osteoclasts

Kang

Moon

et al. 2014

J Dent Res

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Osteoprotegerin (OPG) is secreted by stromal and osteoblastic lineage cells and inhibits osteoclastogenesis by preventing the interaction of receptor activator of nuclear factor-κB ligand (RANKL) with receptor activator of nuclear factor-κB (RANK). In this study, the expression of OPG in osteoclasts themselves and its biological functions during osteoclastogenesis were investigated for the first time. OPG expression in vivo in the developing rat maxilla was examined by immunofluorescence analysis. OPG expression in osteoclasts during in vitro osteoclastogenesis was determined by reverse-transcription polymerase chainreaction (RT-PCR), Western blot, and immunofluorescence staining. We determined the function of OPG produced by osteoclasts during osteoclastogenesis by silencing the OPG gene. The effects of OPG on bone-resorbing activity and apoptosis of mature osteoclasts were examined by the assay of resorptive pit formation on calcium-phosphate-coated plate and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining, respectively. In the immunofluorescence findings, strong immunoreactivities were unexpectedly seen in multinucleated tartrateresistant acid phosphatase (TRAP)-positive osteoclasts around the growing and erupting tooth germs in the rat alveolar bone. In vitro, OPG expression was significantly increased during the differentiation of osteoclasts from mouse bone-marrow-derived cells treated with a combination of macrophage colony-stimulating factor (M-CSF) and RANKL. Interestingly, it was found that OPG small interfering (si)RNA treatment during osteoclastogenesis enhanced the sizes of osteoclasts, but attenuated their boneresorbing activity. Also, the increased chromosomal DNA fragmentation and caspase-3 activity in the late phase of osteoclastogenesis were found to be decreased by treatment with OPG siRNA. Furthermore, effects of OPG siRNA treatment on osteoclastogenesis and bone-resorbing activity were recovered by the treatment of exogenous OPG. These results suggest that OPG, expressed by the osteoclasts themselves, may play an auto-regulatory role in the late phase of osteoclastogenesis through the induction of apoptosis.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Osteoprotegerin Expressed by Osteoclasts

Kang

Moon

et al. 2014

J Dent Res

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“…Thus, TRAcP5b down-regulation can explain the observed reduction on bone resorbing activity in Y 1 R −/− cultures. Furthermore, other study have also reported a correlation between osteoclast size and TRAP activity, where giant osteoclast cells showed decreased TRAP activity 28 , which is also consistent with our results.…”

Section: Discussionsupporting

confidence: 93%

Ablation of Y1 receptor impairs osteoclast bone-resorbing activity

Sousa

Conceição

Silva

et al. 2016

Sci Rep

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Y1 receptor (Y1R)-signalling pathway plays a pivotal role in the regulation of bone metabolism. The lack of Y1R-signalling stimulates bone mass accretion that has been mainly attributed to Y1R disruption from bone-forming cells. Still, the involvement of Y1R-signalling in the control of bone-resorbing cells remained to be explored. Therefore, in this study we assessed the role of Y1R deficiency in osteoclast formation and resorption activity. Here we demonstrate that Y1R germline deletion (Y1R−/−) led to increased formation of highly multinucleated (n > 8) osteoclasts and enhanced surface area, possibly due to monocyte chemoattractant protein-1 (MCP-1) overexpression regulated by RANKL-signalling. Interestingly, functional studies revealed that these giant Y1R−/− multinucleated cells produce poorly demineralized eroded pits, which were associated to reduce expression of osteoclast matrix degradation markers, such as tartrate-resistant acid phosphatase-5b (TRAcP5b), matrix metalloproteinase-9 (MMP-9) and cathepsin-K (CTSK). Tridimensional (3D) morphologic analyses of resorption pits, using an in-house developed quantitative computational tool (BonePit), showed that Y1R−/− resorption pits displayed a marked reduction in surface area, volume and depth. Together, these data demonstrates that the lack of Y1Rs stimulates the formation of larger multinucleated osteoclasts in vitro with reduced bone-resorbing activity, unveiling a novel therapeutic option for osteoclastic bone diseases based on Y1R-signalling ablation.

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“…Quantitatively, TRACP activity was found to increase with increasing cell size, whereas the activity of NADH-tetrazolium reductase decreased proportionally [174] . Ciplea and coworkers [173,174] proposed that this change was indicative of degeneration of the giant cells. Since the multinucleated giant cells associated with GCTB are osteoclast-like cells, which are known to generate significant levels of ROS, it is also likely that some form of NOX is expressed on these cells.…”

Section: Giant Cell Tumors Of Bonementioning

confidence: 90%

Role of NADPH Oxidase in Formation and Function of Multinucleated Giant Cells

Quinn

Schepetkin²

2009

J Innate Immun

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Macrophages play essential roles in a wide variety of physiological and pathological processes. One of the unique features of these phagocytic leukocytes is their ability to fuse, forming multinucleated giant cells. Multinucleated giant cells are important mediators of tissue remodeling and repair and are also responsible for removal or sequestration of foreign material, intracellular bacteria and non-phagocytosable pathogens, such as parasites and fungi. Depending on the tissue where fusion occurs and the inflammatory insult, multinucleated giant cells assume distinctly different phenotypes. Nevertheless, the ultimate outcome is the formation of large cells that can resorb bone tissue (osteoclasts) or foreign material and pathogens (giant cells) extracellularly. While progress has been made in recent years, the mechanisms and factors involved in macrophage fusion are still not fully understood. In addition to cytokines and a number of adhesion proteins and receptors, it is becoming increasingly clear that NADPH oxidase-generated reactive oxygen species (ROS) also play an important role in macrophage fusion. In this review, we provide an overview of macrophage multinucleation, with a specific focus on the role of NADPH oxidases and ROS in macrophage fusion and in the function of multinucleated giant cells. In addition, we provide an updated overview of the role of these cells in inflammation and various autoimmune diseases.

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Size Dependent Enzyme Activities of Multinucleated (Osteoclastic) Giant Cells in Bone Tumors

Cited by 10 publications

References 35 publications

Osteoprotegerin Expressed by Osteoclasts

Osteoprotegerin Expressed by Osteoclasts

Ablation of Y1 receptor impairs osteoclast bone-resorbing activity

Role of NADPH Oxidase in Formation and Function of Multinucleated Giant Cells

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