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 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 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 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.

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 N-acetylcysteine promotes osteogenic differentiation in periodontal ligament stem cells under cyclic mechanical stretch

2021 ◽  
Author(s):  
Xun Xi ◽  
Zixuan Li ◽  
Yi Zhao ◽  
Hong Liu ◽  
Shuai Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Osteogenic Differentiation ◽  
Periodontal Ligament ◽  
Alveolar Bone ◽  
Tooth Movement ◽  
Orthodontic Tooth Movement ◽  
Mechanical Stretch ◽  
Micro Ct ◽  
Periodontal Ligament Stem Cells ◽  
Ct System

Abstract Background Biomechanical forces are vital for the regulation of skeletal tissue. Mechanical stretch plays a vital role in osteogenic differentiation of periodontal ligament stem cells (PDLSCs) during orthodontic treatment. Cyclic mechanical stretch may trigger the up-regulated production of reactive oxygen species (ROS). ROS has a critical effect on bone cell function and the pathophysiology of bone diseases. N-acetylcysteine (NAC), a ROS scavenger, possesses powerful antioxidant capacity. The aim of this study was to determine the role of ROS and NAC in PDLSCs during osteogenic differentiation under cyclic mechanical stretch. We further investigated that the therapeutic potential of NAC to improve the changes of the microstructure of alveolar bone during orthodontic tooth movement in rats by micro-CT system. Methods The expression of COL1 (collagen type I), RUNX2 (runt-related transcription factor 2) and OPN (osteopontin) by qRT-PCR and Western blot experiments, and alkaline phosphatase (ALP) staining as well as ALP activity tests were used to examine osteogenic differentiation tendency of PDLSCs subjected to cyclic mechanical stretch of 10% and 0.5Hz deformation induced by the Flexcell tension system. ROS production in PDLSCs were measured under cyclic mechanical stretch by Flow Cytometry. The levels of reduced glutathione (GSH), oxidized GSH (GSSG) and the GSH/GSSG ratio with or without NAC treatment were analyzed. And we evaluated the changes of the microstructure of alveolar bone during orthodontic tooth movement in rats employing micro-CT system. Results NAC treatment could promote the osteogenic differentiation of PDLSCs under cyclic mechanical stretch. Down-regulated ROS generation and the up-regulated level of GSH and the ratio of GSH/GSSG in PDLSCs treated with NAC were observed in response to cyclic mechanical stretch. NAC improved the microstructure of alveolar bone, including BV/TV (bone volume/total volume), Tb.Th (trabecular thickness), Tb.Sp (trabecular separation) and SMI (microstructure model index), during orthodontic tooth movement in rats. Conclusion These results revealed that NAC might be a potential therapeutic approach for the remodeling of the alveolar bone during orthodontic tooth movement.

scholarly journals Enhanced Osteogenic Differentiation of Periodontal Ligament Stem Cells Using a Graphene Oxide-Coated Poly(ε-caprolactone) Scaffold

Polymers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 797
Author(s):  
Jiyong Park ◽  
Sangbae Park ◽  
Jae Eun Kim ◽  
Kyoung-Je Jang ◽  
Hoon Seonwoo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Graphene Oxide ◽  
Osteogenic Differentiation ◽  
Periodontal Ligament ◽  
Oxygen Plasma ◽  
Alveolar Bone ◽  
Water Soluble ◽  
Periodontal Ligament Stem Cells ◽  
3D Printed

Periodontal diseases occur through bacterial infection in the oral cavity, which can cause alveolar bone loss. Several efforts have been made to reconstruct alveolar bone, such as grafting bone substitutes and 3D-printed scaffolds. Poly(ε-caprolactone) (PCL) is biocompatible and biodegradable, thus demonstrating its potential as a biomaterial substitute; however, it is difficult for cells to adhere to PCL because of its strong hydrophobicity. Therefore, its use as a biomaterial has limitations. In this study, we used graphene oxide (GO) as a coating material to promote the osteogenic differentiation ability of PCL scaffolds. First, 3D-printed PCL scaffolds were fabricated, and the oxygen plasma treatment and coating conditions were established according to the concentration of GO. The physical and chemical properties of the prepared scaffolds were evaluated through water contact angle analysis, Raman spectroscopy, and image analysis. In addition, the adhesion and proliferation of periodontal ligament stem cells (PDLSCs) on the GO scaffolds were assessed via the water-soluble tetrazolium salt-1 (WST-1) assay, and the osteogenic differentiation ability was evaluated through alizarin red S staining. The results confirmed that the cell proliferation and osteogenic differentiation of the PDLSCs were enhanced in the scaffolds coated with oxygen plasma and GO. In conclusion, the plasma-treated GO-coating method that we developed can be used to promote the cell proliferation and osteogenic differentiation of the scaffolds.

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