scholarly journals Long Noncoding RNA Expression Profiles of Periodontal Ligament Stem Cells from the Periodontitis Microenvironment in Response to Static Mechanical Strain

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Jia Liu ◽  
Yan Zhao ◽  
Qiannan Niu ◽  
Ni Qiu ◽  
Shuangyun Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Periodontal Ligament ◽  
Noncoding Rna ◽  
Tooth Movement ◽  
Expression Profiles ◽  
Mechanical Strain ◽  
Pathological State ◽  
Periodontal Ligament Stem Cells ◽  
Periodontal Tissues ◽  
Static Mechanical

During the period of orthodontic tooth movement, periodontal ligament stem cells (PDLSCs) play an important role in transducing mechanical stimulation and tissue remodeling. However, our previous studies verified that the periodontitis microenvironment causes damage to the biological functions of PDLSCs and abnormal mechanical sensitivity. Long noncoding RNAs (lncRNAs) participate in the inflammatory pathogenesis and development of many diseases. Whether lncRNAs are abnormally expressed in PDLSCs obtained from periodontal tissues of periodontitis patients (PPDLSCs) and whether putative lncRNAs participate in the mechanotransductive process in PDLSCs remain poorly understood. First, we subjected PDLSCs obtained from healthy periodontal tissues (HPDLSCs) and PPDLSCs to static mechanical strain (SMS) with 12% elongation at 0.1 Hz frequency using an FX-4000T system and screened overall lncRNA profiles in both cell types by microarray. Among lncRNAs with a fold change   FC > 20.0 , 27 lncRNAs were upregulated in strained HPDLSCs, and 16 lncRNAs (9 upregulated and 7 downregulated) were detected in strained PPDLSCs. For mRNAs with FC > 20.0 , we detected 25 upregulated mRNAs and one downregulated mRNA in strained HPDLSCs and 7 upregulated and 5 downregulated mRNAs in strained PPDLSCs. Further enrichment analysis showed that, unlike HPDLSCs with annotations principally involving transduction-associated signaling pathways, dysregulated mRNAs in PPDLSCs are mainly responsible for pathological conditions. Moreover, coexpressed lncRNA-mRNA networks confirmed the pathological state and exacerbated inflammatory conditions in strained PPDLSCs. Taken together, when compared with strained HPDLSCs, various lncRNAs and mRNAs were dysregulated in PPDLSCs under mechanical forces, implicating the response of lncRNAs in PPDLSCs to mechanical stress. Moreover, we provide potential lncRNA targets, which may contribute to future intervention strategies for orthodontic treatment in periodontitis patients.

scholarly journals Periodontal Ligament Stem Cells in the Periodontitis Microenvironment Are Sensitive to Static Mechanical Strain

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Jia Liu ◽  
Qiang Li ◽  
Shiyu Liu ◽  
Jie Gao ◽  
Wen Qin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Inflammatory Cytokines ◽  
Periodontal Ligament ◽  
Mechanical Strain ◽  
Pathological Process ◽  
Mechanical Force ◽  
Periodontal Ligament Stem Cells ◽  
Periodontal Tissues ◽  
Function Impairment ◽  
Static Mechanical

During orthodontic treatment, periodontium remodeling of periodontitis patients under mechanical force was abnormal. We have previously confirmed the function impairment of periodontal ligament stem cells (PDLSCs) in the periodontitis microenvironment which might be involved in this pathological process. However, the response of PDLSCs in periodontitis microenvironment to mechanical force remains unclear. Therefore, in the present study, we introduced a Flexcell tension apparatus and investigated the response of PDLSCs obtained from periodontal tissues of periodontitis patients (PPDLSCs) and of those obtained from healthy periodontal tissues (HPDLSCs) to different magnitudes of static mechanical strain (SMS). PPDLSCs showed increased proliferation, decreased osteogenic activity, activated osteoclastogenesis, and greater secretion of inflammatory cytokines. Different magnitudes of SMS exerted distinct effects on HPDLSCs and PPDLSCs. An SMS of 12% induced optimal effects in HPDLSCs, including the highest proliferation, the best osteogenic ability, the lowest osteoclastogenesis, and the lowest secretion of inflammatory cytokines, while the optimal SMS for PPDLSCs was 8%. Excessive SMS damaged PPDLSCs function, including decreased proliferation, an imbalance between osteogenesis and osteoclastogenesis, and an activated inflammatory response. Our data suggest that PPDLSCs are more sensitive and less tolerant to SMS, and this may explain why mechanical force results in undesirable effects in periodontitis patients.

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 Mechanical stress potentiates the differentiation of periodontal ligament stem cells into keratocytes

2018 ◽  
Vol 102 (4) ◽  
pp. 562-569 ◽  
Author(s):  
Jialin Chen ◽  
Wei Zhang ◽  
Ludvig J Backman ◽  
Peyman Kelk ◽  
Patrik Danielson
Keyword(s):  
Stem Cells ◽  
Mechanical Stimulation ◽  
Periodontal Ligament ◽  
Synergistic Effects ◽  
Mechanical Strain ◽  
Cell Sheet ◽  
Corneal Stroma ◽  
Cell Sheets ◽  
Periodontal Ligament Stem Cells ◽  
Gene And Protein Expression

AimsTo explore the role of corneal-shaped static mechanical strain on the differentiation of human periodontal ligament stem cells (PDLSCs) into keratocytes and the possible synergistic effects of mechanics and inducing medium.MethodsPDLSCs were exposed to 3% static dome-shaped mechanical strain in a Flexcell Tension System for 3 days and 7 days. Keratocyte phenotype was determined by gene expression of keratocyte markers. Keratocyte differentiation (inducing) medium was introduced in the Flexcell system, either continuously or intermittently combined with mechanical stimulation. The synergistic effects of mechanics and inducing medium on keratocyte differentiation was evaluated by gene and protein expression of keratocyte markers. Finally, a multilamellar cell sheet was assembled by seeding PDLSCs on a collagen membrane and inducing keratocyte differentiation. The transparency of the cell sheet was assessed, and typical markers of native human corneal stroma were evaluated by immunofluorescence staining.ResultsDome-shaped mechanical stimulation promoted PDLSCs to differentiate into keratocytes, as shown by the upregulation of ALDH3A1, CD34, LUM, COL I and COL V. The expression of integrins were also upregulated after mechanical stimulation, including integrin alpha 1, alpha 2, beta 1 and non-muscle myosin II B. A synergistic effect of mechanics and inducing medium was found on keratocyte differentiation. The cell sheets were assembled under the treatment of mechanics and inducing medium simultaneously. The cell sheets were transparent, multilamellar and expressed typical markers of corneal stroma.ConclusionDome-shaped mechanical stimulation promotes differentiation of PDLSCs into keratocytes and has synergistic effects with inducing medium. Multilamellar cell sheets that resemble native human corneal stroma show potential for future clinical applications.

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 Comprehensive analysis of the long noncoding RNA-associated competitive endogenous RNA network in the osteogenic differentiation of periodontal ligament stem cells

BMC Genomics ◽  
2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Lingzhi Lai ◽  
Zhaodan Wang ◽  
Yihong Ge ◽  
Wei Qiu ◽  
Buling Wu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Long Noncoding Rna ◽  
Periodontal Ligament ◽  
Messenger Rna ◽  
Noncoding Rna ◽  
Periodontal Regeneration ◽  
Tgf Beta ◽  
Periodontal Ligament Stem Cells ◽  
Cerna Network ◽  
Significant Expression

Abstract Backgroud The mechanism implicated in the osteogenesis of human periodontal ligament stem cells (PDLSCs) has been investigated for years. Previous genomics data analyses showed that long noncoding RNA (lncRNA), microRNA (miRNA) and messenger RNA (mRNA) have significant expression differences between induced and control human PDLSCs. Competing for endogenous RNAs (ceRNA), as a widely studied mechanism in regenerative medicine, while rarely reported in periodontal regeneration. The key lncRNAs and their ceRNA network might provide new insights into molecular therapies of periodontal regeneration based on PDLSCs. Results Two networks reflecting the relationships among differentially expressed RNAs were constructed. One ceRNA network was composed of 6 upregulated lncRNAs, 280 upregulated mRNAs, and 18 downregulated miRNAs. The other network contained 33 downregulated lncRNAs, 73 downregulated mRNAs, and 5 upregulated miRNAs. Functional analysis revealed that 38 GO terms and 8 pathways related with osteogenesis were enriched. Twenty-four osteogenesis-related gene-centred lncRNA-associated ceRNA networks were successfully constructed. Among these pathways, we highlighted MAPK and TGF-beta pathways that are closely related to osteogenesis. Subsequently, subnetworks potentially linking the GO:0001649 (osteoblast differentiation), MAPK and TGF-beta pathways were constructed. The qRT-PCR validation results were consistent with the microarray analysis. Conclusion We construct a comprehensively identified lncRNA-associated ceRNA network might be involved in the osteogenesis of PDLSCs, which could provide insights into the regulatory mechanisms and treatment targets of periodontal regeneration.

scholarly journals lncRNA HHIP-AS1 Promotes the Osteogenic Differentiation Potential and Inhibits the Migration Ability of Periodontal Ligament Stem Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Qianyi Qin ◽  
Haoqing Yang ◽  
Chen Zhang ◽  
Xiao Han ◽  
Jing Guo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Osteogenic Differentiation ◽  
Bone Remodeling ◽  
Signaling Pathway ◽  
Periodontal Ligament ◽  
Tooth Movement ◽  
Periodontal Ligament Stem Cells ◽  
Differentiation Potential ◽  
Alveolar Bone Remodeling ◽  
Compressive Pressure

Alveolar bone remodeling under orthodontic force is achieved by periodontal ligament stem cells (PDLSCs), which are sensitive to mechanical loading. How to regulate functions of PDLSCs is a key issue in bone remodeling during orthodontic tooth movement. This study is aimed at investigating the roles of lncRNA Hedgehog-interacting protein antisense RNA 1 (HHIP-AS1) in the functional regulation of PDLSCs. First, HHIP-AS1 expression was downregulated in PDLSCs under continuous compressive pressure. Then, we found that the alkaline phosphatase activity, in vitro mineralization, and expression levels of bone sialoprotein, osteocalcin, and osterix were increased in PDLSCs by HHIP-AS1. The results of scratch migration and transwell chemotaxis assays revealed that HHIP-AS1 inhibited the migration and chemotaxis abilities of PDLSCs. In addition, the RNA sequencing data showed that 356 mRNAs and 14 lncRNAs were upregulated, including receptor tyrosine kinase-like orphan receptor 2 and nuclear-enriched abundant transcript 1, while 185 mRNAs and 6 lncRNAs were downregulated, including fibroblast growth factor 5 and LINC00973, in HHIP-AS1-depleted PDLSCs. Bioinformatic analysis revealed several biological processes and signaling pathways related to HHIP-AS1 functions, including the PI3K-Akt signaling pathway and JAK-STAT signaling pathway. In conclusion, our findings indicated that HHIP-AS1 was downregulated in PDLSCs under compressive pressure, and it promoted the osteogenic differentiation potential and inhibited the migration and chemotaxis abilities of PDLSCs. Thus, HHIP-AS1 may be a potential target for accelerating tooth movement during orthodontic treatment.

scholarly journals Rutin promotes osteogenic differentiation of periodontal ligament stem cells through the GPR30-mediated PI3K/AKT/mTOR signaling pathway

2020 ◽  
Vol 245 (6) ◽  
pp. 552-561 ◽  
Author(s):  
Bin Zhao ◽  
Yixuan Xiong ◽  
Yunpeng Zhang ◽  
Linglu Jia ◽  
Wenjing Zhang ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Stem Cells ◽  
Osteogenic Differentiation ◽  
Periodontal Ligament ◽  
Signal Pathway ◽  
Basic Knowledge ◽  
Periodontal Ligament Stem Cells ◽  
Periodontal Tissues ◽  
Phosphorylated Akt ◽  
Differentiation And Proliferation

Rutin is one of the flavonoids found in fruits and vegetables. Recent reports have revealed that rutin is a major player in proliferation and bone development. However, data on how rutin regulates the proliferation of periodontal ligament stem cells (PDLSCs), as well as the differentiation of osteogenic cells are scanty. Here, our findings showed that rutin enhanced PDLSCs proliferation, increased ALP activity, and matrix mineralization. Moreover, rutin significantly promoted the expression of osteogenic genes and elevated phosphorylated AKT and mTOR. Treatment with LY294002 reversed these effects by inhibiting PI3K. We also found that the expression levels of GPR30 were increased by rutin. Interestingly, this upregulation was not altered after the addition of LY294002. In addition, G15, a selective antagonist of GPR30, could reduce the beneficial effects induced by rutin and interfere with the modulation of PI3K/AKT/mTOR signal transduction. Collectively, our findings revealed that rutin increased proliferation and osteogenic differentiation of PDLSCs through GPR30-mediated PI3K/AKT/mTOR signal transduction. Therefore, it could be deduced that rutin as a certain flavonoid possesses therapeutic value for periodontal bone regeneration and tissue engineering. Impact statement In our study, the effects and mechanisms of rutin on the osteogenic differentiation and proliferation of PDLSCs were investigated. Our findings might provide basic knowledge and guidance to understand and use rutin in the bioengineering of the periodontal tissues and regeneration of bones. The following is a short description of the main findings: rutin promotes the osteogenic differentiation and proliferation of PDLSCs; PI3K/AKT/mTOR signal pathway mediates the effects of rutin on PDLSCs; rutin activates PI3K/AKT/mTOR signal pathway via GPR30.

Sign in / Sign up

Export Citation Format

Share Document