Ex vivo bone morphogenetic protein 2 gene delivery using periodontal ligament stem cells for enhanced re-osseointegration in the regenerative treatment of peri-implantitis

Park, Shin‐Young; Kim, Kyoung-Hwa; Gwak, Eun-Hye; Rhee, Sang-Hoon; Lee, Jeong-Cheol; Shin, Soo Young; Koo, Ki‐Tae; Lee, Yong-Moo; Seol, Yang‐Jo

doi:10.1002/jbm.a.35145

Cited by 59 publications

(89 citation statements)

References 32 publications

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“…In addition, PDLSCs show characteristics of mesenchymal stem cells. In addition to STRO-1 and CD146 expression, these cells also express CD105/14/44/106/166/106/166 (Tang et al, 2014;Park et al, 2015). Therefore, flow cytometry was applied to identify stem cell markers on PDLSCs.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia enhances periodontal ligament stem cell proliferation via the MAPK signaling pathway

He¹,

Cao²,

Zhang³

et al. 2016

Genet. Mol. Res.

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ABSTRACT. There is high incidence of periodontal disease in highaltitude environments; hypoxia may influence the proliferation and clone-forming ability of periodontal ligament stem cells (PDLSCs). The MAPK signaling pathway is closely correlated with cell proliferation, differentiation, and apoptosis. Thus, we isolated and cultured PDLSCs under hypoxic conditions to clarify the impact of hypoxia on PDLSC proliferation and the underlying mechanism. PDLSCs were separated and purified by the limiting dilution method and identified by flow cytometry. PDLSCs were cultured under hypoxic or normoxic conditions to observe their cloning efficiency. PDLSC proliferation at different oxygen concentrations was evaluated by MTT assay. Expression of p38/MAPK and MAPK/ERK signaling pathway members was detected by western blotting. Inhibitors for p38/MAPK or ERK were applied to PDLSCs to observe their impacts on clone formation and proliferation. Isolated PDLSCs exhibited typical stem cell morphological characteristics, strong abilities of globular clone formation and proliferation, and upregulated expression of mesenchymal stem cell markers. Stem cell marker expression was not statistically different between PDLSCs cultured under hypoxia and normoxia (P > 0.05). The clone number in the hypoxia group was significantly higher than that in the control (P < 0.05). PDLSC proliferation under hypoxia was higher than that of the control (P < 0.001). p38 and ERK1/2 phosphorylation in hypoxic PDLSCs was markedly enhanced compared to that in the control (P < 0.05). Either P38/MAPK inhibitor or ERK inhibitor treatment reduced clone formation and proliferation. Therefore, hypoxia enhanced PDLSC clone formation and proliferation by activating the p38/MAPK and ERK/MAPK signaling pathways.

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Section: Discussionmentioning

confidence: 99%

Hypoxia enhances periodontal ligament stem cell proliferation via the MAPK signaling pathway

He¹,

Cao²,

Zhang³

et al. 2016

Genet. Mol. Res.

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“…Platelet concentration products, which are autologous constituents of inductive factors obtained from blood, have been known high concentrations of platelets containing various growth factors 1) . Marx reported that the combined use of autogeneous bon e wi th P R P was inc rease d in radi ograp h ic an d histomorphometric bone density 2) .…”

Section: Introductionmentioning

confidence: 99%

Effects of Plasma Rich in Growth Factors on Bone Formation in Rat Calvaria

Eda

Takahashi

Iwai

et al. 2015

J. Hard Tissue Biology.

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Abstruct: Plasma rich in growth factors (PRGF) had been used in regenerative therapy such as soft tissue and newly bone formation. However, there has been little basic research into the efficacy of PRGF in bone regeneration. In this study, we evaluated the efficacy for new bone formation by transplantation of PRGF onto rat calvaria. The osteogenic potential was evaluated by histologic findings, immunohistochemistry and bone formation analyzed with micro-computed tomography (micro-CT). PRGF was prepared by centrifugation of rat whole blood (WB), and then was activated using 10% calcium chloride solution. The activated PRGF transplanted within a polytetrafluoroethylene (PTFE) tube was transplanted onto calvarial bone of rats. Histological observation demonstrated that PRGF group showed newly formed bone in a wide range. Immunohistochemistry showed Runx2, Osterix, Bone Alkaline Phosphatase (BAP) and Osteocalcin expressed in PRGF group during the early stage of bone formation. Micro-CT showed that PRGF group promoted an increase in bone volume which compared to control group. We concluded that PRGF has more capacity for bone regeneration, and PRGF may be useful in bone regeneration treatment.

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“…Moreover, several studies have shown that dental-derived MSCs have greater differentiation capacities compared with BMMSCs [9,10,11]. Among the published studies that focused on the osteogenic capability of PDLSCs, one previous study demonstrated a therapeutic potential for autologous PDLSCs by demonstrating significantly increased new bone formation around peri-implantitis defects in an experimental animal model [12]. Indeed, in a comparative experiment to test the bone regeneration capacity of dental-derived MSCs, PDLSCs encouraged more mineralization in the calvarial defects than gingival mesenchymal stem cells (GMSCs), which exhibit less osteogenic differentiation ability in specific stem cell delivery systems [13].…”

Section: Introductionmentioning

confidence: 99%

Increased Osteogenic Differentiation of Periodontal Ligament Stem Cells on Polydopamine Film Occurs via Activation of Integrin and PI3K Signaling Pathways

Lee

An³

et al. 2014

Cell Physiol Biochem

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Background/Aims: Mussel-inspired polydopamine (PDA) is known to be an effective bioadhesive and bioactive material for controlling stem cell fate, which is important in stem cell-based regenerative medicine; however, the effect of PDA on osteogenic differentiation of periodontal ligament stem cells (PDLSCs) is not fully understood. In this study, we investigated the osteoinductive effect of PDA on PDLSCs and examined how this phenomenon is encouraged. Methods: Osteogenic induction of PDLSCs was established by culturing cells on PDA film or on an uncoated polystyrene surface as a control. Osteogenic differentiation of PDLSCs was assessed by measurement of intracellular calcium levels and alkaline phosphatase (ALP) activity as well as by evaluation of protein expression of osteocalcin (OCN), osterix (OSX), and runt-related transcription factor 2 (RUNX2). Results: The PDLSCs cultured on PDA film showed higher osteogenic activity than those on the control surface. Moreover, PDLSCs on PDA film expressed increased levels of the integrin adhesion receptors integrin α5 and β1 compared to control cells. Expression of one isoform of the intracellular signaling protein phosphatidylinositol-3-kinase (PI3K), p110γ, was increased in PDLSCs on PDA film in a PDA dose-dependent manner. This signaling protein was found to interact with integrin β1, demonstrating integrin-linked PI3K activation in response to PDA. Finally, the blockage of PI3K reduced the PDA-induced osteogenic activity of PDLSCs. Conclusion: our findings suggest that the bioadhesive PDA stimulates osteogenic differentiation of PDLSCs via activation of the integrin α5/β1 and PI3K signaling pathways.

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Ex vivo bone morphogenetic protein 2 gene delivery using periodontal ligament stem cells for enhanced re-osseointegration in the regenerative treatment of peri-implantitis

Cited by 59 publications

References 32 publications

Hypoxia enhances periodontal ligament stem cell proliferation via the MAPK signaling pathway

Hypoxia enhances periodontal ligament stem cell proliferation via the MAPK signaling pathway

Effects of Plasma Rich in Growth Factors on Bone Formation in Rat Calvaria

Increased Osteogenic Differentiation of Periodontal Ligament Stem Cells on Polydopamine Film Occurs via Activation of Integrin and PI3K Signaling Pathways

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