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 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 Synergistic effects triggered by simultaneous Toll‐like receptor‐2 and ‐3 activation in human periodontal ligament stem cells

2019 ◽  
Vol 90 (10) ◽  
pp. 1190-1201 ◽  
Author(s):  
Alice Blufstein ◽  
Christian Behm ◽  
Johannes Gahn ◽  
Oksana Uitz ◽  
Ivana Naumovska ◽  
...  
Keyword(s):  
Stem Cells ◽  
Periodontal Ligament ◽  
Synergistic Effects ◽  
Toll Like Receptor ◽  
Periodontal Ligament Stem Cells ◽  
Toll Like Receptor 2

scholarly journals Protease-Activated Receptor Type 1 Activation Enhances Osteogenic Activity in Human Periodontal Ligament Stem Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Emanuel Silva Rovai ◽  
Lucas Macedo Batitucci Ambrósio ◽  
Bruno Nunes de França ◽  
Letícia Rodrigues de Oliveira ◽  
Letícia Miquelitto Gasparoni ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Protein Expression ◽  
Periodontal Ligament ◽  
Calcium Concentration ◽  
Periodontal Ligament Stem Cells ◽  
Osteogenic Activity ◽  
Gene And Protein Expression ◽  
New Strategy ◽  
Calcium Deposits

Protease-activated receptor 1 (PAR1) has been associated to tissue repair and bone healing. The aim of the present study was to evaluate the effect of PAR1 activation on the osteogenic activity of human periodontal ligament stem cells (PDLSCs). PDLSCs were cultured in the presence of PAR1-selective agonist peptide (100 nM), thrombin (0.1 U/mL), or PAR1 antagonist peptide (100 nM). Calcium deposits, calcium concentration (supernatant), alkaline phosphatase activity (ALP), cell proliferation, and gene (qPCR) and protein expression (ELISA assay) of osteogenic factors were assessed at 2, 7, and 14 days. PAR1 activation led to increased calcium deposits (p<0.05), calcium concentration (p<0.05), ALP activity (p<0.05), and cell proliferation (p<0.05). Further, PAR1 activation may increase gene and protein expression of Runx2 (p<0.05) and OPG (p<0.05). In conclusion, PAR1 activation increases osteogenic activity of PDLSCs, providing a possible new strategy for periodontal regenerative therapies.

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.

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