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

2018 ◽  
Vol 19 (12) ◽  
pp. 3843 ◽  
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.

scholarly journals Force-Induced Autophagy in Periodontal Ligament Stem Cells Modulates M1 Macrophage Polarization via AKT Signaling

2021 ◽  
Vol 9 ◽  
Author(s):  
Nan Jiang ◽  
Danqing He ◽  
Yushi Ma ◽  
Junxiang Su ◽  
Xiaowen Wu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Remodeling ◽  
Periodontal Ligament ◽  
Tooth Movement ◽  
Macrophage Polarization ◽  
Akt Signaling ◽  
Mechanical Force ◽  
Akt Signaling Pathway ◽  
Periodontal Ligament Stem Cells ◽  
M1 Macrophage

Autophagy, a lysosomal degradation pathway, serves as a protective cellular mechanism in maintaining cell and tissue homeostasis under mechanical stimulation. As the mechanosensitive cells, periodontal ligament stem cells (PDLSCs) play an important role in the force-induced inflammatory bone remodeling and tooth movement process. However, whether and how autophagy in PDLSCs influences the inflammatory bone remodeling process under mechanical force stimuli is still unknown. In this study, we found that mechanical force stimuli increased the expression of the autophagy protein LC3, the number of M1 macrophages and osteoclasts, as well as the ratio of M1/M2 macrophages in the compression side of the periodontal ligament in vivo. These biological changes induced by mechanical force were repressed by the application of an autophagy inhibitor 3-methyladenine. Moreover, autophagy was activated in the force-loaded PDLSCs, and force-stimulated PDLSC autophagy further induced M1 macrophage polarization in vitro. The macrophage polarization could be partially blocked by the administration of autophagy inhibitor 3-methyladenine or enhanced by the administration of autophagy activator rapamycin in PDLSCs. Mechanistically, force-induced PDLSC autophagy promoted M1 macrophage polarization via the inhibition of the AKT signaling pathway. These data suggest a novel mechanism that force-stimulated PDLSC autophagy steers macrophages into the M1 phenotype via the AKT signaling pathway, which contributes to the inflammatory bone remodeling and tooth movement process.

scholarly journals TRIM16 Positively Regulates Osteogenic Differentiation of Human Periodontal Ligament Stem Cells by Modulating the Ubiquitination and Degradation of RUNX2

2020 ◽  
Author(s):  
Yi Zhao ◽  
Qiaoli Zhai ◽  
Hong Liu ◽  
Xun Xi ◽  
Shuai Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Alkaline Phosphatase ◽  
Bone Regeneration ◽  
Osteogenic Differentiation ◽  
Periodontal Ligament ◽  
Osteogenic Potential ◽  
Common Disease ◽  
Periodontal Ligament Stem Cells ◽  
Alizarin Red ◽  
Periodontal Tissues

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.

scholarly journals Mesenchymal stem cell-derived extracellular vesicles alter disease outcomes via endorsement of macrophage polarization

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Jiangmei Wang ◽  
Jie Xia ◽  
Ruoqiong Huang ◽  
Yaoqin Hu ◽  
Jiajie Fan ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Stromal Cells ◽  
Macrophage Polarization ◽  
Critical Role ◽  
Cell Contact ◽  
Central Nervous System Diseases ◽  
The Past ◽  
Disease Outcomes ◽  
M2 Polarization ◽  
M1 Polarization

Abstract Mesenchymal stem cells (MSCs) are adult stromal cells that reside in virtually all postnatal tissues. Due to their regenerative and immunomodulatory capacities, MSCs have attracted growing attention during the past two decades. MSC-derived extracellular vesicles (MSC-EVs) are able to duplicate the effects of their parental cells by transferring functional proteins and genetic materials to recipient cells without cell-to-cell contact. MSC-EVs also target macrophages, which play an essential role in innate immunity, adaptive immunity, and homeostasis. Recent studies have demonstrated that MSC-EVs reduce M1 polarization and/or promote M2 polarization in a variety of settings. In this review, we discuss the mechanisms of macrophage polarization and roles of MSC-EV-induced macrophage polarization in the outcomes of cardiovascular, pulmonary, digestive, renal, and central nervous system diseases. In conclusion, MSC-EVs may become a viable alternative to MSCs for the treatment of diseases in which inflammation and immunity play a critical role.

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

2019 ◽  
Vol 28 (15) ◽  
pp. 1037-1049 ◽  
Author(s):  
Alina Čebatariūnienė ◽  
Karolina Kriaučiūnaitė ◽  
Justina Prunskaitė ◽  
Virginijus Tunaitis ◽  
Augustas Pivoriūnas
Keyword(s):  
Stem Cells ◽  
Extracellular Vesicles ◽  
Periodontal Ligament ◽  
Periodontal Ligament Stem Cells

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

2019 ◽  
Vol 10 ◽  
Author(s):  
Jacopo Pizzicannella ◽  
Agnese Gugliandolo ◽  
Tiziana Orsini ◽  
Antonella Fontana ◽  
Alessia Ventrella ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Regeneration ◽  
Extracellular Vesicles ◽  
Periodontal Ligament ◽  
Periodontal Ligament Stem Cells

scholarly journals Extracellular Vesicles of Human Periodontal Ligament Stem Cells Contain MicroRNAs Associated to Proto-Oncogenes: Implications in Cytokinesis

2020 ◽  
Vol 11 ◽  
Author(s):  
Luigi Chiricosta ◽  
Serena Silvestro ◽  
Agnese Gugliandolo ◽  
Guya Diletta Marconi ◽  
Jacopo Pizzicannella ◽  
...  
Keyword(s):  
Stem Cells ◽  
Extracellular Vesicles ◽  
Periodontal Ligament ◽  
Periodontal Ligament Stem Cells

scholarly journals The Role of Noncoding RNAs in Osteogenic Differentiation of Human Periodontal Ligament Stem Cells

2021 ◽  
Vol 6 ◽  
pp. 247275122199922
Author(s):  
Paras Ahmad ◽  
Martin J. Stoddart ◽  
Elena Della Bella
Keyword(s):  
Stem Cells ◽  
Osteogenic Differentiation ◽  
Periodontal Ligament ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Alveolar Bone ◽  
Noncoding Rnas ◽  
Tissue Destruction ◽  
Periodontal Ligament Stem Cells ◽  
Periodontal Tissues

Chronic inflammatory diseases, including periodontitis, are the most common causes of bone tissue destruction. Periodontitis often leads to loss of connective tissue homeostasis and reduced alveolar bone levels. Human periodontal ligament stem cells (PDLSCs), a population of multipotent stem cells derived from periodontal ligament tissues, are considered as candidate cells for the regeneration of alveolar bone and periodontal tissues. Periodontitis impairs the osteogenic differentiation of human PDLSCs. Noncoding RNAs (ncRNAs), including long noncoding RNA (lncRNA), microRNA (miRNA), and circular RNA (circRNA), have been proposed as vital regulators influencing several differentiation processes including bone regeneration. Still, the molecular mechanisms of ncRNAs regulating osteogenic differentiation of human PDLSCs remain poorly understood. Exploring the influence of ncRNAs in the process of osteogenic differentiation of human PDLSCs may provide novel therapeutic strategies for tissue regeneration as the regeneration of the lost periodontium is the ultimate goal of periodontal therapy.

scholarly journals TRIM16 Promotes Osteogenic Differentiation of Human Periodontal Ligament Stem Cells by Modulating CHIP-Mediated Degradation of RUNX2

2021 ◽  
Vol 8 ◽  
Author(s):  
Yi Zhao ◽  
Qiaoli Zhai ◽  
Hong Liu ◽  
Xun Xi ◽  
Shuai Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Regeneration ◽  
Osteogenic Differentiation ◽  
Periodontal Ligament ◽  
Critical Role ◽  
Nodule Formation ◽  
Periodontal Ligament Stem Cells ◽  
Protein Levels ◽  
Periodontal Tissues ◽  
Short Hairpin Rnas

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, an E3 ubiquitin ligase, is downregulated in periodontal tissues of patients with periodontitis, while the role of TRIM16 in the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) is largely unknown. Firstly, we found that TRIM16 was increased throughout the osteogenic media induced differentiation of hPDLSCs. Then overexpression plasmids and specific short-hairpin RNAs (shRNAs) were constructed to manipulate the expression of target molecules. TRIM16 significantly promoted alkaline phosphatase activity, mineralized nodule formation, and positively regulated the expression of osteo-specific markers RUNX2, COL1A1 and OCN except the mRNA of RUNX2. Mechanistically, TRIM16 serves as a pivotal factor that stabilizes RUNX2 protein levels by decreasing CHIP-mediated K48-linked ubiquitination degradation of the RUNX2 protein. This study identified a novel mechanism of TRIM16 in regulating stability of the RUNX2 protein, which promoted the osteogenic differentiation of hPDLSCs. TRIM16 may be a potential target of stem cell based-bone regeneration for periodontal therapies.

scholarly journals Mechanobiology of Periodontal Ligament Stem Cells in Orthodontic Tooth Movement

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Huaming Huang ◽  
Ruili Yang ◽  
Yan-heng Zhou
Keyword(s):  
Stem Cells ◽  
Periodontal Ligament ◽  
Tooth Movement ◽  
Critical Role ◽  
Orthodontic Tooth Movement ◽  
Periodontal Ligament Stem Cells ◽  
Orthodontic Force ◽  
Applied Forces

Periodontal ligament stem cells (PDLSCs) possess self-renewal, multilineage differentiation, and immunomodulatory properties. They play a crucial role in maintaining periodontal homeostasis and also participated in orthodontic tooth movement (OTM). Various studies have applied controlled mechanical stimulation to PDLSCs and investigated the effects of orthodontic force on PDLSCs. Physical stimuli can regulate the proliferation and differentiation of PDLSCs. During the past decade, a variety of studies has demonstrated that applied forces can activate different signaling pathways in PDLSCs, including MAPK, TGF-β/Smad, and Wnt/β-catenin pathways. Besides, recent advances have highlighted the critical role of orthodontic force in PDLSC fate through mediators, such as IL-11, CTHRC1, miR-21, and H2S. This perspective review critically discusses the PDLSC fate to physical forcein vitroand orthodontic forcein vivo, as well as the underlying molecular mechanism involved in OTM.

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