Expression of Vascular Endothelial Growth Factor and the Effects on Bone Remodeling during Experimental Tooth Movement

Kohno, Satoru; Kaku, Masato; Tsutsui, K.; Motokawa, Masaharu; Ohtani, Junji; Tenjo, Kaoru; Tohma, Yuiko; Tokimasa, Chiyoko; Fujita, Tsuyoshi; Kawata, Toshitsugu; Tanne, Kazuo

doi:10.1177/154405910308200306

Cited by 79 publications

(72 citation statements)

References 25 publications

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“…18 Several experimental approaches have been attempted to induce more efficient tooth movement by increasing the number of osteoclasts and the resultant bone resorption. Simultaneous administration of 1,25(OH) 2 D 3 , 17 osteocalcin, 19 PGE, 20 vascular endothelial growth factor, 21 and application of mechanical force induces the differentiation of osteoclasts, enhancing bone resorption and resulting in faster tooth movement than those produced by mechanical force alone. Furthermore, it has been observed that bone resorption in response to IL-1 or TNF is accompanied by an increase in osteoclast number.…”

Section: Discussionmentioning

confidence: 99%

Epidermal Growth Factor in Liposomes May Enhance Osteoclast Recruitment during Tooth Movement in Rats

Saddi¹,

Alves²,

Paulino³

et al. 2008

The Angle Orthodontist

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Objective: To evaluate the effects of local administration of epidermal growth factor (EGF) located within liposomes on recruitment of osteoclasts during mechanical force in rats. Materials and Methods: An orthodontic elastic band was inserted between the left upper first and second molars, to move mesially the first molar. Rats were randomly divided into 4 groups (n ϭ 8): EGF (2 ng/L) located within liposomes (group 1), liposomes only (group 2), soluble EGF (2 ng/L; group 3), or vehicle alone (group 4). The solutions were injected into the region of the root furcation of the left first molar after elastic band insertion. Tooth movement was measured using a plaster model of the maxilla, and the number of osteoclasts recruited at the pressure side of the first molar was histologically evaluated. Results: Intergroup analysis showed that there was no significant difference between group 2 and group 4 (P Ͼ .05) and between group 1 and group 3 (P Ͼ .05). However, group 1 and group 3 exhibited greater differences in tooth movement than group 2 and group 4 (P Ͻ .05). On the other hand, group 1 showed greater tooth movement than groups 2 and 4 with statistical significance (P Ͻ .01). The increase in the number of osteoclasts in group 1 was significantly higher than in the other groups (P Ͻ .05). Conclusion: Exogenous EGF-liposome administration has an additive effect when compared with soluble EGF on the rate of osteoclast recruitment, producing faster bone resorption and tooth movement.

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Section: Discussionmentioning

confidence: 99%

Epidermal Growth Factor in Liposomes May Enhance Osteoclast Recruitment during Tooth Movement in Rats

Saddi¹,

Alves²,

Paulino³

et al. 2008

The Angle Orthodontist

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“…To investigate the activation of ERK1/2 and NF-κB pathway, mouse OCPs were cultured in α-modified MEM with 0.1% FBS and without M-CSF for 24 h. Then, the cells were treated with by injection of rhVEGF (11,12). Moreover, it has been reported that VEGF, expressed by periodontal ligament fibroblasts, may also induce angiogenesis in a process involving mechanical stimuli (25).…”

Section: Protein Extraction and Western Blotting Procedures For Analymentioning

confidence: 99%

“…Orthodontic tooth movement and related tissue remodeling are achieved by osteoclastic bone resorption followed by osteoblastic new bone formation. Our recent study has demonstrated that VEGF is expressed by osteoblasts located on the tension side of the alveolar bone during experimental tooth movement (12). Furthermore, the number of osteoclasts and the amount of tooth movement were enhanced Seika, Tokyo, Japan), 250 μg/mL amphotericin B (Nacalai Tesque, Kyoto, Japan), 60 μg/mL kanamycin (Meiji Seika) and 50 ng/mL rhM-CSF (R&D Systems Inc., Minneapolis, USA) at 37°C in a humidified atmosphere of 5% CO 2 .…”

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confidence: 99%

Fms-like tyrosine kinase (Flt)-4 signaling participates in osteoclast differentiation in osteopetrotic (op/op) mice

et al. 2009

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Vascular endothelial growth factor (VEGF) induces osteoclast differentiation as well as neovascularization by binding to the fms-like tyrosine kinase (Flt)-1 and fetal liver kinase (Flk)-1 receptors. The Flt-4 receptor also plays an important role in angiogenesis and lymphangiogenesis. The purpose of this study was to investigate the functions of Flt-4 in the signaling pathway of osteoclast differentiation. We examined the expression of Flt-4 on osteoclast precursor cells (OCPs), and the ability of recombinant human (rh) VEGF-D, one of the ligands of Flt-4, to stimulate the phosphorylation of extracellular-regulated kinase1/2 (ERK1/2) and to activate the nuclear factor-kappa B (NF-κB) pathway in OCPs. The number of osteoclasts induced by injection of rhVEGF-D in osteopetrotic (op/op) mice was also evaluated in the absence or presence of neutralizing antibodies to Flt-4. Flt-4 expression was detected on OCPs at both gene and protein levels and stimulation of Flt-4 by rhVEGF-D might induce activation of mitogen-activated protein kinase (MAPK) and NF-κB pathways for induction of osteoclast differentiation. Moreover, the number of osteoclasts in op/op mice increased after injection of rhVEGF-D, but was significantly reduced by the injection of Flt-4 neutralizing antibodies. We have therefore shown that Flt-4 expressed on OCPs, might activate MAPK and NF-κB pathways and played an important role in osteoclast differentiation.Vascular endothelial growth factor (VEGF) can induce neovascularization (15). Two specific tyrosine kinase receptors for VEGF have been identified, namely the fms-like tyrosine kinase (Flt)-1 and fetal liver kinase (Flk)-1 which are specifically expressed on vascular endothelial cells and mature osteoclasts (4,16,19). Furthermore, previous studies have demonstrated that recombinant human (rh) VEGF can induce the production of a large number of osteoclasts in osteopetrotic (op/op) mice (17). These mice are characterized by a deficiency in osteoclasts, monocytes, and macrophages that is caused by the absence of a functional macrophage-colony stimulating factor (M-CSF) (6,10,17,22,23). These findings indicate that the VEGF signaling pathway leading to osteoclast differentiation involves signaling through both of these VEGF receptors. Orthodontic tooth movement and related tissue remodeling are achieved by osteoclastic bone resorption followed by osteoblastic new bone formation. Our recent study has demonstrated that VEGF is expressed by osteoblasts located on the tension side of the alveolar bone during experimental tooth movement (12). Furthermore, the number of osteoclasts and the amount of tooth movement were enhanced

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“…It has been reported that VEGF is detected in periodontal tissues during experimental tooth movement, and that the local injection of VEGF enhances the number of osteoclasts and increases the rate of tooth movement (29,30). The effect of anti-VEGF polyclonal antibody markedly decreased the number of osteoclasts and suppressed the amount of tooth movement and the relapse of moved teeth (31).…”

Section: Discussionmentioning

confidence: 99%

Mechanical stress up-regulates RANKL expression via the VEGF autocrine pathway in osteoblastic MC3T3-E1 cells

Nakai

Yoshimura²,

Deyama³

et al. 2009

Mol Med Rep

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Expression of Vascular Endothelial Growth Factor and the Effects on Bone Remodeling during Experimental Tooth Movement

Cited by 79 publications

References 25 publications

Epidermal Growth Factor in Liposomes May Enhance Osteoclast Recruitment during Tooth Movement in Rats

Epidermal Growth Factor in Liposomes May Enhance Osteoclast Recruitment during Tooth Movement in Rats

Fms-like tyrosine kinase (Flt)-4 signaling participates in osteoclast differentiation in osteopetrotic (op/op) mice

Mechanical stress up-regulates RANKL expression via the VEGF autocrine pathway in osteoblastic MC3T3-E1 cells

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