Vascular endothelial growth factor receptors in osteoclast differentiation and function

Aldridge, Stephen; Lennard, T. W. J.; Williams, John A.; Birch, Mark

doi:10.1016/j.bbrc.2005.07.145

Cited by 88 publications

(72 citation statements)

References 26 publications

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“…23,24 Conflicting evidence exists as to whether VEGF-A can support osteoclast formation. [17][18][19]21,22 Our findings are in agreement with studies showing that VEGF-A can correct the defect in op/op mice and support a role for VEGF-A in osteoclast formation. Although VEGF-A has previously been reported to support human osteoclast formation in vitro by Aldridge et al, 21 this was not conclusively shown as osteoclastogenesis was not determined in the presence of an anti-M-CSF antibody and resorption was noted in negative control cultures.…”

Section: Discussionsupporting

confidence: 91%

“…We noted that osteoclasts formed in VEGF-Atreated cultures were capable of much less resorption (7.5% relative to M-CSF-treated cultures) and did not observe a difference in the number of TRAP þ multinucleated cells. Osteoclast formation and lacunar resorption in our M-CSFtreated cultures was considerably more (65-80% compared with 4-8%) than in the study of Aldridge et al 21 FL has previously been shown in vitro to support osteoclast formation independently of M-CSF in mice (including op/ op mice), but not in man. 17,21 Our findings indicate that FL can support human osteoclast formation; less resorption and fewer osteoclasts were observed compared with M-CSFtreated cultures.…”

Section: Discussioncontrasting

confidence: 73%

“…Osteoclast formation and lacunar resorption in our M-CSFtreated cultures was considerably more (65-80% compared with 4-8%) than in the study of Aldridge et al 21 FL has previously been shown in vitro to support osteoclast formation independently of M-CSF in mice (including op/ op mice), but not in man. 17,21 Our findings indicate that FL can support human osteoclast formation; less resorption and fewer osteoclasts were observed compared with M-CSFtreated cultures. Our findings also confirm previous studies, which showed that HGF can support human osteoclast formation.…”

Section: Discussioncontrasting

confidence: 73%

“…There is contradictory evidence as to whether VEGF and FL independently support osteoclastogenesis. 17,[20][21][22] In this study we have analysed the effect of M-CSF and M-CSF substitute growth factors, both alone and in combination, on human monocyte-osteoclast differentiation. In addition, we have examined whether these growth factors are expressed in GCTB and whether they influence osteoclast cytomorphology and resorption activity.…”

mentioning

confidence: 99%

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VEGF, FLT3 ligand, PlGF and HGF can substitute for M-CSF to induce human osteoclast formation: implications for giant cell tumour pathobiology

Taylor

Kashima

Knowles

et al. 2012

Laboratory Investigation

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Giant cell tumour of bone (GCTB) is a primary bone tumour that contains numerous very large, hyper-nucleated osteoclastic giant cells. Osteoclasts form from CD14 þ monocytes and macrophages in the presence of receptor activator of nuclear factor kappa B ligand (RANKL) and macrophage-colony stimulating factor (M-CSF). GCTB contains numerous growth factors, some of which have been reported to influence osteoclastogenesis and resorption. We investigated whether these growth factors are capable of substituting for M-CSF to support osteoclast formation from cultured human monocytes and whether they influence osteoclast cytomorphology and resorption. Vascular endothelial growth factor-A (VEGF-A), VEGF-D, FLT3 ligand (FL), placental growth factor (PlGF) and hepatocyte growth factor (HGF) supported RANKL-induced osteoclastogenesis in the absence of M-CSF, resulting in the formation of numerous TRAP þ multinucleated cells capable of lacunar resorption. Monocytes cultured in the presence of M-CSF, HGF, VEGF-A and RANKL together resulted in the formation of very large, hyper-nucleated (GCTB-like) osteoclasts that were hyper-resorptive. M-CSF and M-CSF substitute growth factors were identified immunohistochemically in GCTB tissue sections and these factors stimulated the resorption of osteoclasts derived from a subset of GCTBs. Our findings indicate that there are growth factors that are capable of substituting for M-CSF to induce human osteoclast formation and that these factors are present in GCTB where they influence osteoclast cytomorphology and have a role in osteoclast formation and resorption activity. The osteoclast is a multinucleated cell, which is formed from circulating mononuclear phagocyte precursors derived from the bone marrow. 1,2 It exhibits a number of specialised cytochemical and functional features, including the ability to carry out lacunar bone resorption. Increased osteoclast formation and activity is seen in a number of osteolytic bone and joint conditions, including notably giant cell tumour of bone (GCTB), a primary bone tumour, which contains numerous, very large, often hyper-nucleated osteoclastic giant cells that effect a considerable amount of bone resorption. 3,4 Osteoclast differentiation from monocyte or macrophage precursors requires the presence of receptor activator of nuclear factor kappa B ligand (RANKL) and macrophage-colony stimulating factor (M-CSF). 5 The importance of M-CSF in osteoclast formation is evidenced by the fact that in op/op osteopetrotic mice, which have a mutation in the M-CSF gene, very few osteoclasts are found in bone and there is markedly decreased bone resorption. 6,7 M-CSF promotes several aspects of osteoclastogenesis including the proliferation and fusion of osteoclast precursors as well as osteoclasts and the expression of the RANKL receptor by these cells. [8][9][10] The effect of M-CSF on mature osteoclast resorption activity is controversial with both a decrease and increase in lacunar resorption being reported. [11][12][13] Although bone resorption is gre...

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Section: Discussionsupporting

confidence: 91%

Section: Discussioncontrasting

confidence: 73%

Section: Discussioncontrasting

confidence: 73%

mentioning

confidence: 99%

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VEGF, FLT3 ligand, PlGF and HGF can substitute for M-CSF to induce human osteoclast formation: implications for giant cell tumour pathobiology

Taylor

Kashima

Knowles

et al. 2012

Laboratory Investigation

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“…VEGF is essential for bone formation through upregulation of osteoclastic function and promotion of osteoclast differentiation and survival [24][25][26]. Thus, inhibition of VEGF might hinder repair of physical trauma [19].…”

Section: Introductionmentioning

confidence: 99%

Bevacizumab and osteonecrosis of the jaw: incidence and association with bisphosphonate therapy in three large prospective trials in advanced breast cancer

Guarneri

Miles

Robert³

et al. 2010

Breast Cancer Res Treat

243

150

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Long-term bisphosphonate therapy is associated with increased risk of osteonecrosis of the jaw (ONJ). In a retrospective analysis, a 16% ONJ incidence was reported in patients receiving bisphosphonates with antiangiogenic therapy (bevacizumab or sunitinib) for bone metastases from breast, colon, or renal cell cancers. To assess ONJ incidence with bevacizumab, we analysed data from 3,560 patients receiving bevacizumab-containing therapy for locally recurrent or metastatic breast cancer (LR/MBC) in two double-blind, randomised trials (AVADO and RIBBON-1) and a large, non-randomised safety study (ATHENA). The overall incidence of ONJ with bevacizumab was 0.3% in the blinded phase of the two randomised trials and 0

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Association of Acroosteolysis With Enhanced Osteoclastogenesis and Higher Blood Levels of Vascular Endothelial Growth Factor in Systemic Sclerosis

Park

Fava

Carrino

et al. 2015

Arthritis & Rheumatology

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Objective Bone resorption of distal phalanges or acro-osteolysis (AO) can develop in systemic sclerosis (SSc) causing pain and functional limitation. We investigated whether AO may be associated with abnormal osteoclastogenesis in SSc patients and whether hypoxia may be involved in this process. Methods Peripheral blood mononuclear cells (PBMCs) obtained from 26 SSc patients (11 with and 15 without AO) and 14 healthy controls (HC) were cultured in the presence of receptor activator of NF-κB-ligand (RANKL) and macrophage colony-stimulating factor for 9 days. Tartrate resistant acid phosphatase (TRAP)+ multinucleated giant cells (MNGs) containing 3 or more nuclei were counted as osteoclasts (OCs). Plasma levels and effects of vascular endothelial growth factor (VEGF) on OC formation were evaluated. Results SSc patients with AO formed significantly more OCs after 9 days than did subjects without AO (142.4±67.0 vs. 27.2±17.6 MNGs/well, p<0.001) or HC (18.7±27.0 MNGs/well, p <0.001). No significant difference in OC formation was noted between the patients without AO and HC. Plasma levels of VEGF were higher in SSc patients with AO compared to those without (142.4± 69.6 pg/mL vs. 88.1±38.2 pg/mL, p<0.001) or HC (54.2±24.6 pg/mL, p=0.018). Priming with VEGF-A for 24 hours significantly increased OC generation by 5.3±1.9 fold (p=0.03). The radiographic extent of AO was associated with increased OC formation (Spearman rho=0.741, p=0.01). Conclusion Increased OC formation and higher VEGF levels may contribute to AO in SSc patients.Further studies are needed to elucidate whether targeting osteoclastogenesis may provide a specific therapeutic option for SSc-AO.

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Vascular endothelial growth factor receptors in osteoclast differentiation and function

Cited by 88 publications

References 26 publications

VEGF, FLT3 ligand, PlGF and HGF can substitute for M-CSF to induce human osteoclast formation: implications for giant cell tumour pathobiology

VEGF, FLT3 ligand, PlGF and HGF can substitute for M-CSF to induce human osteoclast formation: implications for giant cell tumour pathobiology

Bevacizumab and osteonecrosis of the jaw: incidence and association with bisphosphonate therapy in three large prospective trials in advanced breast cancer

Association of Acroosteolysis With Enhanced Osteoclastogenesis and Higher Blood Levels of Vascular Endothelial Growth Factor in Systemic Sclerosis

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