Monoclonal antibodies to human osteoclasts

Norton, Melissa; Lewis, D.; McNulty, Katrina; Pringle, J.; Chambers, I J.

doi:10.1016/8756-3282(85)90025-0

Cited by 7 publications

(9 citation statements)

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“…We also detected vitronectin receptor (integrin avb3) on the transformed cells using the monoclonal antibody 23C6 (Horton et al, 1985); this is often expressed upon human melanomas and has been implicated in the aggressiveness of these tumours (Seftor et al, 1992). For most clones the staining with the 23C6 antibody increased upon v-Myb inactivation indicating di erentiation, but decreased in the absence of EGF again suggesting the maintenance of an undifferentiated phenotype (Figure 5f).…”

Section: Undi Erentiated Cells Express Markers Characteristic Of the mentioning

confidence: 98%

v-Myb can transform and regulate the differentiation of melanocyte precursors

Bell

Frampton

1999

Oncogene

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The activity of the c-Myb transcription factor is essential for the development of de®nitive multi-and uni-lineage progenitors of the haemopoietic system. Re¯ecting this requirement, c-Myb has been oncogenically activated by transduction in the E26 avian retrovirus which elicits an acute leukaemia by transforming haemopoietic progenitors. Here, we report the novel ®nding that Myb in cooperation with EGF receptor signalling can be used to generate clonally expanded populations of transformed cells which have the phenotype of melanocyte precursors. Through the use of a conditional temperature sensitive mutant of Myb, we show that in the transformed cells Myb regulates commitment to melanocyte di erentiation and possibly proliferation. These results add to our understanding of the roles of c-Myb beyond the haemopoietic system and to our knowledge and means of investigating the importance of transcription factors in the melanocyte linage.

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Section: Undi Erentiated Cells Express Markers Characteristic Of the mentioning

confidence: 98%

v-Myb can transform and regulate the differentiation of melanocyte precursors

Bell

Frampton

1999

Oncogene

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“…After 1 h, the number of adhered cells was quantified by measuring the absorbance at 450 nm (26). Anti-human ␣v␤3 monoclonal antibody, 23C6 (Serotec, Oxford, UK), was used to examine the contribution of ␣v␤3 integrin (27). EILDVPST peptide (Funakoshi, Tokyo, Japan), originating from the CS-1 site of fibronectin (28), was used to examine the contribution of the CS-1 site to the cell adhesion to fibronectin.…”

Section: Methodsmentioning

confidence: 99%

A Novel Peptide Motif for Platelet Fibrinogen Receptor Recognition

Katada

Hayashi

Sato

et al. 1997

Journal of Biological Chemistry

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To develop a specific antagonist of platelet ␣IIb␤3 using small linear peptides, we synthesized a series of hexapeptides that did not have an Arg-Gly-Asp (RGD) sequence and examined their anti-platelet activity and their specificity for ␣IIb␤3. We found a novel motif sequence, Pro-X1-X2-X3-Asp-X4, where X1 to X4 were all L-form ␣-amino acids, which specifically inhibited aggregation of human platelets at submicromolar concentrations. The Pro residue at the N terminus was essential to the anti-platelet activity, and the acetylation of the imino group of this residue also resulted in the complete loss of the activity. The results of the binding assay using purified human platelet ␣IIb␤3 and placental ␣v␤3 and those of the cell adhesion assay suggest that this motif peptide is highly specific for platelet ␣IIb␤3 among other integrins. Flow cytometric studies using an fluorescein isothiocyanate-labeled RGD peptide showed that this motif peptide inhibited the binding of an RGD peptide to activated platelets, suggesting that it has the same inhibitory mode as RGD peptides. Conformational analysis of this motif peptide and an RGD-containing peptide suggests that the imino group of the Pro residue may substitute for the role of the guanidino group of the Arg residue of the RGD sequence.Integrins are heterodimeric cell surface receptor molecules and are thought to be particularly important mediators of cell adhesion, cell migration, and adhesion-dependent intracellular signaling. Until now, more than 20 integrin receptors have been identified, and many of them recognize the Arg-Gly-Asp (RGD) 1 sequence as a common recognition motif within their putative ligands upon ligand-receptor interaction (1-4). The ligand binding specificity has been studied by many investigators, and it has been revealed that some integrins show apparent redundancy in integrin-ligand interactions. For example, ␣v␤3, a so-called vitronectin receptor, can bind several apparently dissimilar ligands such as vitronectin, fibrinogen, fibronectin, von Willebrand factor, osteopontin, and bone sialoprotein, all of which have the RGD sequence (reviewed in Refs. 5 and 6). In addition, the same RGD site within a ligand can be recognized by several different integrins. These apparent redundancies in integrin-ligand interactions are very interesting aspects of integrin receptors and may be beneficial to the cell adhesion of many types of cells to extracellular matrix proteins.We are interested in developing small peptides that are specific for each integrin as a tool for investigating ligandintegrin interactions and as an agent for therapeutic uses. Recently, many small peptides containing the RGD sequence have been synthesized, and their specificity toward integrins has been examined (7,8). Most of the linear RGD peptides have shown very low specificity among many types of integrin receptors including platelet ␣IIb␤3 (fibrinogen receptor), ␣v␤3 (vitronectin receptor), and ␣5␤1 (fibronectin receptor). In the case of ␣IIb␤3 and ␣v␤3, both integrins have the same...

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“…Cell preparations on coverslips were also stained immunohistochemically, using an indirect immunoperoxidase technique with the monoclonal antibody 23C6 (Serotec, Oxford, UK): this is directed against CD51, the vitronectin receptor (VNR), a highly osteoclast-associated antigen (Horton et al 1985). Cell preparations were similarly stained with the monoclonal antibody GRS1, directed against CD14, a macrophage-associated antigen not known to be expressed by osteoclasts (Athanasou & Quinn 1990).…”

Section: Histochemical and Immunohistochemical Characterisation Of Cumentioning

confidence: 99%

Effect of corticosteroids on human osteoclast formation and activity

Hirayama¹,

Sabokbar²,

Athanasou³

2002

Journal of Endocrinology

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Chronic corticosteroid treatment is known to induce bone loss and osteoporosis. Osteoclasts are specialised boneresorbing cells that are formed from mononuclear phagocyte precursors that circulate in the monocyte fraction. In this study we have examined the effect of the synthetic glucocorticoid, dexamethasone, on human osteoclast formation and bone-resorbing activity. Human monocytes were cultured for up to 21 days on glass coverslips and dentine slices, with soluble receptor activator for nuclear factor B ligand (RANKL; 30 ng/ml) and human macrophage-colony stimulating factor (M-CSF; 25 ng/ml) in the presence and absence of dexamethasone (10 8 M). The addition of dexamethasone over a period of 7 and 14 days of culture of monocytes (during which cell proliferation and differentiation predominantly occurred) resulted in a marked increase in the formation of tartrate-resistant acid phosphatase-positive multinucleated cells and an increase in lacunar resorption. The addition of dexamethasone to monocyte cultures after 14 days (when resorptive activity of osteoclasts had commenced) reduced the extent of lacunar resorption compared with cultures to which no dexamethasone had been added. The addition of dexamethasone to osteoclasts isolated from giant cell tumours of bone significantly inhibited resorption pit formation. Our findings indicate that dexamethasone has a direct effect on osteoclast formation and activity, stimulating the proliferation and differentiation of human osteoclast precursors and inhibiting the bone-resorbing activity of mature osteoclasts.

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Monoclonal antibodies to human osteoclasts

Cited by 7 publications

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v-Myb can transform and regulate the differentiation of melanocyte precursors

v-Myb can transform and regulate the differentiation of melanocyte precursors

A Novel Peptide Motif for Platelet Fibrinogen Receptor Recognition

Effect of corticosteroids on human osteoclast formation and activity

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