Enamel Matrix Derivative Protein Stimulated Wound Healing via Phosphoinositide 3‐Kinase

Goda, Seiji; Kaneshita, Yuki; Inoue, Hiroshi; Domae, Eisuke; Ikeo, Takashi; Iida, Joji; Domae, Naochika

doi:10.1902/jop.2009.090127

Cited by 7 publications

(7 citation statements)

References 35 publications

(60 reference statements)

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“…Previous reports have shown that EMD enhances the phosphorylation of ERK, p38MAPK, JNK, and Akt in human gingival fibroblasts . The effects of SB203580, U0126, SP600125, and LY294002 on EMD‐induced VEGF production were examined.…”

Section: Resultsmentioning

confidence: 99%

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Enamel matrix derivative induces production of vascular endothelial cell growth factor in human gingival fibroblasts

Sakoda

Nakajima

Noguchi

2012

European J Oral Sciences

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Enamel matrix derivative (EMD) may enhance periodontal wound healing by inducing angiogenesis. We sought to investigate the effect and the mechanism of action of EMD on vascular endothelial growth factor (VEGF) production by human gingival fibroblasts. Cells were stimulated with EMD, transforming growth factor-β1 (TGF-β1), or fibroblast growth factor 2 (FGF-2), with or without antibodies to TGF-β1 or FGF-2. The levels of VEGF in the culture media were measured using an ELISA. We examined the effects of SB203580 [a p38 mitogen-activated protein kinase (MAPK) inhibitor], U0126 [an extracellular signal-regulated kinase (ERK) inhibitor], SP600125 [a c-Jun N-terminal kinase (JNK) inhibitor], and LY294002 [a phosphatidylinositol 3-kinase (PI3K)/Akt inhibitor] on EMD-induced VEGF production. Enamel matrix derivative stimulated the production of VEGF in a dose- and time-dependent manner. Treatment of human gingival fibroblasts with antibodies to TGF-β1 or FGF-2 significantly decreased EMD-induced VEGF production, whereas the addition of exogenous TGF-β1 and FGF-2 stimulated VEGF production. Enamel matrix derivative-induced VEGF production was significantly attenuated by SB203580, U0126, and LY294002. Our results suggest that EMD stimulates VEGF production partially via TGF-β1 and FGF-2 in human gingival fibroblasts and that EMD-induced VEGF production is regulated by ERK, p38 MAPK, and PI3K/Akt pathways. Enamel matrix derivative-induced production of VEGF by human gingival fibroblasts may be involved in the enhancement of periodontal wound healing by inducing angiogenesis.

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Section: Resultsmentioning

confidence: 99%

“…Furthermore, Goda et al . demonstrated that the activation of PI3K plays a key role in EMD‐stimulated osteoblast migration. Here, we found that EMD‐induced VEGF production was potently suppressed by inhibitors of ERK and p38, and only slightly by a PI3K inhibitor (Fig.…”

Section: Discussionmentioning

confidence: 99%

Enamel matrix derivative induces production of vascular endothelial cell growth factor in human gingival fibroblasts

Sakoda

Nakajima

Noguchi

2012

European J Oral Sciences

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“…Enamel matrix derivative was added to cultures of periodontal ligament cells or osteoblasts in which an in vitro wound had been created, and wound‐fill was measured together with other parameters, including some signaling pathways , to show that it enhances ‘ in vitro wound healing’.…”

Section: In Vitro Models Of Periodontal Regenerationmentioning

confidence: 99%

In vitro models for evaluation of periodontal wound healing/regeneration

Weinreb¹,

Nemcovsky²

2015

Periodontology 2000

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Periodontal wound healing and regeneration are highly complex processes, involving cells, matrices, molecules and genes that must be properly choreographed and orchestrated. As we attempt to understand and influence these clinical entities, we need experimental models to mimic the various aspects of human wound healing and regeneration. In vivo animal models that simulate clinical situations of humans can be costly and cumbersome. In vitro models have been devised to dissect wound healing/regeneration processes into discrete, analyzable steps. For soft tissue (e.g. gingival) healing, in vitro models range from simple culture of cells grown in monolayers and exposed to biological modulators or physical effectors and materials, to models in which cells are 'injured' by scraping and subsequently the 'wound' is filled with new or migrating cells, to three-dimensional models of epithelial-mesenchymal recombination or tissue explants. The cells employed are gingival keratinocytes, fibroblasts or endothelial cells, and their proliferation, migration, attachment, differentiation, survival, gene expression, matrix production or capillary formation are measured. Studies of periodontal regeneration also include periodontal ligament fibroblasts or progenitors, osteoblasts or osteoprogenitors, and cementoblasts. Regeneration models measure cellular proliferation, attachment and migration, as well as gene expression, transfer and differentiation into a mineralizing phenotype and biomineralization. Only by integrating data from models on all levels (i.e. a single cell to the whole organism) can various critical aspects of periodontal wound healing/regeneration be fully evaluated.

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“…The PI3K/AKT/mTOR signaling pathway is a major signaling pathway involved in cell proliferation, apoptosis and metastasis, and its cascade reaction pathway occupies an important position in the signal transduction process (16). As a member of the lipid kinase family, PI3K is a heterodimer composed of two subunits, including a regulatory and a catalytic subunit (17). At rest, PI3K is ubiquitous in the cytosol.…”

Section: Introductionmentioning

confidence: 99%

Tanshinone IIA enhances the inhibitory effect of imatinib on proliferation and motility of acute leukemia cell line TIB‑152 in�vivo and in�vitro by inhibiting the PI3K/AKT/mTOR signaling pathway

Teng¹,

Xu²,

Qin³

2019

Oncol Rep

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Acute lymphoblastic leukemia (ALL) is a malignant hematological disease. Tanshinone IIA (Tan IIA) has antitumor activity in vitro and in vivo. The aim of the present study was to investigate the effects of Tan IIA in combination with imatinib (IM) on the proliferation, apoptosis, migration and invasion of acute T lymphocytic leukemia TIB-152 cells in vivo and in vitro, and analyze the potential underlying mechanism. Tan IIA and IM, alone and in combination, significantly inhibited proliferation, migration and invasion of TIB-152 cells, and promoted apoptosis; the effect of co-treatment with Tan IIA plus IM was enhanced. IGF-1 promoted the proliferation, migration and invasion of TIB-152 cells and inhibited apoptosis, while Tan IIA treatment significantly reversed these effects. In vivo experiments demonstrated that treatment with Tan IIA and IM, alone or in combination, significantly inhibited tumor growth in TIB-152 xenograft mice; the growth inhibition of Tan IIA plus IM was the strongest observed. Western blot analysis revealed that the combination of Tan IIA and IM resulted in significantly lower levels of p-PI3K, p-AKT and p-mTOR in cells and tissues compared with the IM and Tan alone treatment groups. In addition, the combination of Tan IIA and IM significantly decreased the levels of Ki67, cleaved caspase-3, VEGF and MMP-9 in cells and tissues, and the level of caspase-3 was significantly increased. Taken together, the results revealed that Tan IIA enhanced the inhibitory effect of imatinib on TIB-152 cell proliferation, migration and invasion, and induced apoptosis, which may be associated with inhibition of the PI3K/AKT/mTOR signaling pathway. Tanshinone IIA enhances the inhibitory effect of imatinib on proliferation and motility of acute leukemia cell line TIB-152 in vivo and in vitro by inhibiting the PI3K/AKT/mTOR signaling pathway

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Enamel Matrix Derivative Protein Stimulated Wound Healing via Phosphoinositide 3‐Kinase

Abstract: These results demonstrated that the activation of PI 3-kinase plays a key role in the EMD protein-stimulated migration of osteoblasts.

Cited by 7 publications

References 35 publications

Enamel matrix derivative induces production of vascular endothelial cell growth factor in human gingival fibroblasts

Enamel matrix derivative induces production of vascular endothelial cell growth factor in human gingival fibroblasts

In vitro models for evaluation of periodontal wound healing/regeneration

Tanshinone IIA enhances the inhibitory effect of imatinib on proliferation and motility of acute leukemia cell line TIB‑152 in�vivo and in�vitro by inhibiting the PI3K/AKT/mTOR signaling pathway

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