CD44 Occupancy Prevents Macrophage Multinucleation

Sterling, Hyacinth; Saginario, Charles; Vignery, Agnès

doi:10.1083/jcb.143.3.837

Cited by 97 publications

(84 citation statements)

References 44 publications

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“…Scattered mononuclear cells positive for CD14 were also noted in these cultures, indicating that not all TAMs showed evidence of osteoclast differentiation. The TRAP þ /VNR þ mononuclear cells were also noted in these cultures; mononuclear cells that exhibit the cytochemical and functional characteristics of osteoclasts have previously been noted in mouse and human macrophage cultures (Sterling et al, 1998;Quinn et al, 2002;Adamopoulos et al, 2006). There was no expression of CD99.…”

Section: Ewing's Sarcoma Tam-osteoclast Differentiationmentioning

confidence: 82%

Cellular and humoral mechanisms of osteoclast formation in Ewing's sarcoma

et al. 2007

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Cellular mechanisms that account for tumour osteolysis associated with Ewing's sarcoma are uncertain. Osteoclasts are marrowderived multinucleated cells (MNCs) that effect tumour osteolysis. Osteoclasts are known to form from macrophages by both receptor activator for nuclear factor-kB (RANK) ligand (RANKL)-dependent and -independent mechanisms. In this study, our aim has been to determine whether tumour-associated macrophages (TAMs) isolated from Ewing's sarcoma are capable of differentiating into osteoclasts and to characterise the cellular and humoral mechanisms whereby this occurs. Tumour-associated macrophages were isolated from two Ewing's sarcomas and cultured on both coverslips and dentine slices for up to 21 days with soluble RANKL and macrophage colony stimulating factor (M-CSF). Osteoclast formation from TAMs (CD14 þ ) was evidenced by the formation of tartrate-resistant acid phosphatase (TRAP) and vitronectin receptor (VNR)-positive MNCs, which were capable of carrying out lacunar resorption. This osteoclast formation was inhibited by the addition of bisphosphonates. Both Ewing's sarcoma-derived fibroblasts and some bone stromal cells expressed RANKL and supported osteoclast formation by a contact-dependent mechanism. We also found that osteoclast differentiation occurred when Ewing's TAMs were cultured with tumour necrosis factor (TNF)-a in the presence of M-CSF and that TC71 Ewing's sarcoma cells stimulated osteoclast formation through the release of a soluble factor, the action of which was abolished by an antibody to TNF-a. These results indicate that TAMs in Ewing's sarcoma are capable of osteoclast differentiation by both RANKL-dependent and TNF-a-dependent mechanisms and that Ewing's sarcoma cells produce osteoclastogenic factor(s). Our findings suggest that anti-resorptive and anti-osteoclastogenic therapies may be useful in inhibiting the osteolysis of Ewing's sarcoma.

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Section: Ewing's Sarcoma Tam-osteoclast Differentiationmentioning

confidence: 82%

Cellular and humoral mechanisms of osteoclast formation in Ewing's sarcoma

et al. 2007

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“…In particular, we would like to know (1) if P2X 7 expression is required on both partner cells (would a P2X 7 ϩ fuse with a P2X 7 Ϫ cell? ); (2) if the pore function of P2X 7 is needed for fusion, or if this receptor, maybe via the bulky extracellular domain, triggers fusion via alternative mechanisms; and more importantly, (3) to what extent P2X 7 is relevant for monocyte/macrophage fusion occurring in vivo in the bone or within inflammatory granulomas.…”

Section: Resultsmentioning

confidence: 99%

“…With the exception of the osteoclasts, to which fusion confers an obvious enhanced capability for resorption of extracellular components, it is not clear why MGCs form, nor is the molecular mechanism known that drives fusion [2]. A few candidate molecules have been proposed, such as LFA-1, ICAM-1, E-cadherins, CD98, and more recently CD44 [3], but it is likely that this complex process involves the coordinate interaction of a large number of membrane receptors needed for cell aggregation, establishment of close cell-to-cell interaction, and finally the actual membrane fusion event.…”

Section: Cytokines Released From Activated T Lymphocytes [Interleukinmentioning

confidence: 99%

ATP receptors and giant cell formation

Virgilio

Falzoni²,

Chiozzi³

et al. 1999

Journal of Leukocyte Biology

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“…Recently, however, two receptors, SIRP␣ (36) and CD44 (37), have been implicated in the fusion process. Indeed, one of the cloning strategies used to identify SIRP␣ used Abs that blocked monocyte-monocyte fusion (36).…”

Section: Discussionmentioning

confidence: 99%

CMRF-35-Like Molecule-1, a Novel Mouse Myeloid Receptor, Can Inhibit Osteoclast Formation

Chung

Humphrey

Nakamura

et al. 2003

The Journal of Immunology

105

116

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By homology to triggering receptor expressed by myeloid cells-2, we screened the mouse expressed sequence tag database and isolated a new single Ig domain receptor, which we have expressed and characterized. The receptor is most similar in sequence to the human CMRF-35 receptor, and thus we have named it CMRF-35-like molecule (CLM)-1. By screening the mouse genome, we determined that CLM-1 was part of a multigene family located on a small segment of mouse chromosome 11. Each contains a single Ig domain, and they are expressed mainly in cells of the myeloid lineage. CLM-1 contains multiple cytoplasmic tyrosine residues, including two that lie in consensus immunoreceptor tyrosine-based inhibitory motifs, and we demonstrate that CLM-1 can associate with Src-homology 2 containing phosphatase-1. Expression of CLM-1 mRNA is down-regulated by treatment with receptor activator of NF-κB ligand (RANKL), a cytokine that drives osteoclast formation. Furthermore, expression of CLM-1 in the osteoclastogenic cell line RAW (RAW.CLM-1) prevents osteoclastogenesis induced by RANKL and TGF-β. RAW.CLM-1 cells fail to multinucleate and do not up-regulate calcitonin receptor, but they express tartrate-resistant acid phosphatase, cathepsin K, and β3 integrin, suggesting that osteoclastogenesis is blocked at a late-intermediate stage. Thus, we define a new family of myeloid receptors, and demonstrate that the first member of this family, CLM-1, is an inhibitory receptor, able to block osteoclastogenesis.

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CD44 Occupancy Prevents Macrophage Multinucleation

Cited by 97 publications

References 44 publications

Cellular and humoral mechanisms of osteoclast formation in Ewing's sarcoma

Cellular and humoral mechanisms of osteoclast formation in Ewing's sarcoma

ATP receptors and giant cell formation

CMRF-35-Like Molecule-1, a Novel Mouse Myeloid Receptor, Can Inhibit Osteoclast Formation

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