Engineered Extracellular Vesicles From Human Periodontal-Ligament Stem Cells Increase VEGF/VEGFR2 Expression During Bone Regeneration

Abstract BackgroundPeriodontal disease is a common disease that compromises the integrity of tooth-supporting tissues. Bone regeneration is the ultimate goal of periodontal therapies, in which osteogenic differentiation of human periodontal ligament stem cells plays a critical role. The tripartite motif (TRIM)16 is downregulated in periodontal tissues of patients with periodontitis and involved in osteogenic differentiation of human bone marrow mesenchymal stem cells(hBMSCs).However, the role of TRIM16 in the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) is largely unknown.MethodshPDLSCs were isolated and identified by immunophenotype assays using flow cytometry. Overexpression plasmids and specific short-hairpin RNAs (shRNAs) were constructed to manipulate the expression of target molecules. Alkaline phosphatase (ALP) staining, alizarin red staining (ARS) and enzyme‐linked immunosorbent assays (ELISA) were used to evaluate osteogenic potential capacity. Reverse transcription quantitative PCR (RT-qPCR) and Western blot analysis were performed to determine the expression of osteogenic-related markers and activation of relevant signaling pathways. Co-immunoprecipitation assays were performed to confirm the interactions between proteins and the ubiquitination of RUNX2. A LC-MS/MS analysis was performed to explore the different expression proteins in present of TRIM16.ResultsTRIM16 significantly promoted alkaline phosphatase activity and mineralized nodule formation, and positively regulated the osteogenic differentiation of hPDLSCs by enhancing protein expression of RUNX2, COL1A1 and OCN. Mechanistically, TRIM16 serves as a pivotal factor that stabilizes RUNX2 protein levels by decreasing CHIP-mediated K48-linked ubiquitination degradation of the RUNX2 protein. Besides, TRIM16 significantly increased expression of COL1A1 via activation of p38MAPK/RUNX2.ConclusionThis study identified a novel mechanism of TRIM16 in regulating stability of the RUNX2 protein, which may promote the osteogenic differentiation of hPDLSCs. TRIM16 may be a potential target of stem cell based-bone regeneration for periodontal therapies.

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Extracellular Vesicles Suppress Basal and Lipopolysaccharide-Induced NFκB Activity in Human Periodontal Ligament Stem Cells

Stem Cells and Development ◽

10.1089/scd.2019.0021 ◽

2019 ◽

Vol 28 (15) ◽

pp. 1037-1049 ◽

Cited By ~ 2

Author(s):

Alina Čebatariūnienė ◽

Karolina Kriaučiūnaitė ◽

Justina Prunskaitė ◽

Virginijus Tunaitis ◽

Augustas Pivoriūnas

Keyword(s):

Stem Cells ◽

Extracellular Vesicles ◽

Periodontal Ligament ◽

Periodontal Ligament Stem Cells

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Guided Bone Regeneration Using Collagen Scaffolds, Growth Factors, and Periodontal Ligament Stem Cells for Treatment of Peri-Implant Bone Defects In Vivo

Stem Cells International ◽

10.1155/2017/3548435 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 13

Author(s):

Peer W. Kämmerer ◽

Malte Scholz ◽

Maria Baudisch ◽

Jan Liese ◽

Katharina Wegner ◽

...

Keyword(s):

Stem Cells ◽

Bone Regeneration ◽

Periodontal Ligament ◽

Bone Growth ◽

Collagen Matrix ◽

Guided Bone Regeneration ◽

Periodontal Ligament Stem Cells ◽

Bone Apposition ◽

Collagen Powder

Introduction. The aim of the study was an evaluation of different approaches for guided bone regeneration (GBR) of peri-implant defects in an in vivo animal model. Materials and Methods. In minipigs (n=15), peri-implant defects around calcium phosphate- (CaP-; n=46) coated implants were created and randomly filled with (1) blank, (2) collagen/hydroxylapatite/β-tricalcium phosphate scaffold (CHT), (3) CHT + growth factor cocktail (GFC), (4) jellyfish collagen matrix, (5) jellyfish collagen matrix + GFC, (6) collagen powder, and (7) collagen powder + periodontal ligament stem cells (PDLSC). Additional collagen membranes were used for coverage of the defects. After 120 days of healing, bone growth was evaluated histologically (bone to implant contact (BIC;%)), vertical bone apposition (VBA; mm), and new bone height (NBH; %). Results. In all groups, new bone formation was seen. Though, when compared to the blank group, no significant differences were detected for all parameters. BIC and NBH in the group with collagen matrix as well as the group with the collagen matrix + GFC were significantly less when compared to the collagen powder group (all: p<0.003). Conclusion. GBR procedures, in combination with CaP-coated implants, will lead to an enhancement of peri-implant bone growth. There was no additional significant enhancement of osseous regeneration when using GFC or PDLSC.

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Estrogen enhances the bone regeneration potential of periodontal ligament stem cells derived from osteoporotic rats and seeded on nano-hydroxyapatite/collagen/poly(L-lactide)

International Journal of Molecular Medicine ◽

10.3892/ijmm.2016.2559 ◽

2016 ◽

Vol 37 (6) ◽

pp. 1475-1486 ◽

Cited By ~ 9

Author(s):

LING-LING E ◽

WEN-HUAN XU ◽

LIN FENG ◽

YI LIU ◽

DONG-QING CAI ◽

...

Keyword(s):

Stem Cells ◽

Bone Regeneration ◽

Periodontal Ligament ◽

Regeneration Potential ◽

Periodontal Ligament Stem Cells

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Human Periodontal Ligament Stem Cells Transplanted with Nanohydroxyapatite/Chitosan/Gelatin 3D Porous Scaffolds Promote Jaw Bone Regeneration in Swine

Stem Cells and Development ◽

10.1089/scd.2020.0204 ◽

2021 ◽

Author(s):

Qing Zhao ◽

Guifeng Li ◽

Tiancong Wang ◽

Yuqin Jin ◽

Wei Lu ◽

...

Keyword(s):

Stem Cells ◽

Bone Regeneration ◽

Periodontal Ligament ◽

Porous Scaffolds ◽

Periodontal Ligament Stem Cells ◽

Jaw Bone

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Lipopolysaccharide-Preconditioned Periodontal Ligament Stem Cells Induce M1 Polarization of Macrophages through Extracellular Vesicles

International Journal of Molecular Sciences ◽

10.3390/ijms19123843 ◽

2018 ◽

Vol 19 (12) ◽

pp. 3843 ◽

Cited By ~ 8

Author(s):

Hyejong Kang ◽

Myung-Ju Lee ◽

Sang Park ◽

Myung-Shin Lee

Keyword(s):

Stem Cells ◽

Extracellular Vesicles ◽

Periodontal Ligament ◽

Macrophage Polarization ◽

Critical Role ◽

Conditioned Media ◽

Common Disease ◽

Tissue Destruction ◽

Periodontal Ligament Stem Cells ◽

M1 Polarization

Periodontitis is a common disease characterized by chronic inflammation and tissue destruction of gums. Human periodontal ligament stem cells (PDLSCs), derived from the periodontium, have stem cell properties similar to those of mesenchymal stem cells. PDLSCs possess not only the potential to differentiate into other tissues, but also immunomodulatory abilities. Macrophages play a critical role in periodontal disease, but little is known regarding the role of PDLSCs in macrophage modulation during inflammation. In this study, we investigated the effect of PDLSCs on the macrophage cell line. While the conditioned media from PDLSCs under normal culture conditions did not affect macrophage polarization, the lipopolysaccharide (LPS)-preconditioned PDLSCs induced significant changes in M1 polarization. Extracellular vesicles (EVs) isolated from the conditioned media of LPS-preconditioned PDLSCs induced strong M1 polarization of macrophages. Additionally, the M1 polarization was abolished by DNase I treatment of EVs. Therefore, the LPS-stimulated PDLSCs induce M1 polarization of macrophages through EVs, suggesting that the EVs from PDLSCs might be a potential therapeutic target for inflammation in the periodontium.

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