Clodronate Inhibits PGE2 Production in Compressed Periodontal Ligament Cells

2006 ◽  
Vol 85 (8) ◽  
pp. 757-760 ◽  
Author(s):  
L. Liu ◽  
K. Igarashi ◽  
H. Kanzaki ◽  
M. Chiba ◽  
H. Shinoda ◽  
...  
Keyword(s):  
Periodontal Ligament ◽  
Tooth Movement ◽  
Orthodontic Tooth Movement ◽  
Periodontal Ligament Cells ◽  
Prostaglandin E ◽  
Rankl Expression ◽  
Inhibitory Effects ◽  
Striking Increase ◽  
Pdl Cells ◽  
Cox 2

Periodontal ligament (PDL) cells play an essential role in orthodontic tooth movement. We recently reported that clodronate, a non-N-containing bisphosphonate, strongly inhibited tooth movement in rats, and thus could be a useful adjunct for orthodontic treatment. However, it is not clear how clodronate affects the responses of PDL cells to orthodontic force. In this study, we hypothesized that clodronate prevents the mechanical stress-induced production of prostaglandin E2 (PGE2), interleukin-1β (IL-1β), and nitric oxide (NO) in human PDL cells. A compressive stimulus caused a striking increase in PGE2 production, while the responses of IL-1β and NO were less marked. Clodronate concentration-dependently inhibited the stress-induced production of PGE2. Clodronate also strongly inhibited stress-induced gene expression for COX-2 and RANKL. These results suggest that the inhibitory effects of clodronate on tooth movement and osteoclasts may be due, at least in part, to the inhibition of COX-2-dependent PGE2 production and RANKL expression in PDL cells.

scholarly journals Compression and Tension Inversely Change Osteoprotegerin Expression via miR-3198 in Periodontal Ligament Cells

2018 ◽  
Author(s):  
Hiroyuki Kanzaki ◽  
Satoshi Wada ◽  
Yuuki Yamaguchi ◽  
Yuta Katsumata ◽  
Kanako Itohiya ◽  
...  
Keyword(s):  
Real Time ◽  
Mirna Expression ◽  
Periodontal Ligament ◽  
Tooth Movement ◽  
Expression Profiles ◽  
Orthodontic Tooth Movement ◽  
Periodontal Ligament Cells ◽  
Rt Pcr ◽  
Pdl Cells ◽  
Mirna Expression Profiles

Background: Osteoclastic bone resorption in the compression zone of periodontal ligament (PDL) plays a role in orthodontic tooth movement, and is regulated by the balance of RANKL and OPG. Compression downregulates OPG, conversely, tension upregulates OPG in PDL cells. However, the regulatory mechanism of OPG expression in PDL cells under different mechanical stresses remains unclear. Methods: To study microRNA (miRNA) expression profiles, compression (2g/cm2) or tension (15%-elongation) was applied to immortalized human PDL (HPL) cells, and miRNA was extracted. The miRNA expression was analyzed using a human miRNA microarray, and the changes of the miRNA expression were confirmed by real-time RT-PCR. In addition, miR-3198-mimic and -inhibitor were transfected into HPL cells to understand the resulting OPG expression and production. Results: Certain miRNAs were expressed differentially under compression and tension. Some miRNAs including miR-3198 were upregulated only by compression. Real-time RT-PCR confirmed that compression induced miR-3198, but tension reduced it, in HPL cells. miR-3198-inhibitor upregulated and miR-3198-mimic reduced OPG in HPL cells. miR-3198-inhibitor rescued the compression-mediated downregulation of OPG. On the other hand, miR-3198-mimic reduced OPG expression under tension. Conclusion: We conclude that miR-3198 is upregulated by compression and is downregulated by tension, suggesting that miR-3198 downregulates OPG in response to mechanical stress.

scholarly journals Compression and hypoxia play independent roles while having combinative effects in the osteoclastogenesis induced by periodontal ligament cells

2015 ◽  
Vol 86 (1) ◽  
pp. 66-73 ◽  
Author(s):  
Mei Le Li ◽  
Jianru Yi ◽  
Yan Yang ◽  
Xuan Zhang ◽  
Wei Zheng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Periodontal Ligament ◽  
Tooth Movement ◽  
Thin Sheet ◽  
Orthodontic Tooth Movement ◽  
Compressive Force ◽  
Periodontal Ligament Cells ◽  
Tartrate Resistant Acid Phosphatase ◽  
Hypoxia Group ◽  
Polymerase Chain

ABSTRACT Objective:  To investigate the isolated and combined effects of compression and hypoxia on the osteoclastogenesis induced by periodontal ligament cells (PDLCs). Materials and Methods:  A periodontal ligament tissue model (PDLtm) was established by 3-D culturing human PDLCs on a thin sheet of poly lactic-co-glycolic acid scaffold. The PDLtm was treated with hypoxia and/or compression for 6, 24, or 72 hours. After that, a real-time polymerase chain reaction was used for gene expression analysis. The conditioned media were used for the coculture of osteoblast and osteoclast (OC) precursors; tartrate-resistant acid phosphatase staining was done to examine OC formation. Results:  Either compression or hypoxia alone significantly up-regulated the gene expression of pro-osteoclastogenic cytokines in the PDLtm and enhanced osteoclastogenesis in the cocultures, and the combination of the two had significantly stronger effects than either stimulation alone. In addition, comparing the two stimulants, we found that the osteoclastogenic property of the PDLCs peaked earlier (at 6 hours) in the compression group than in the hypoxia group (at 24 hours). Conclusions:  Both compressive force and hypoxia may take part in initiating osteoclastogenesis in orthodontic tooth movement and may have combinatory effects, which could update our concepts of the mechanisms involved in the initiation of bone resorption on the pressure side of the tooth in question.

scholarly journals Anabolic Properties of High Mobility Group Box Protein-1 in Human Periodontal Ligament CellsIn Vitro

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Michael Wolf ◽  
Stefan Lossdörfer ◽  
Piero Römer ◽  
Rogerio Bastos Craveiro ◽  
James Deschner ◽  
...  
Keyword(s):  
Periodontal Ligament ◽  
Tooth Movement ◽  
Therapeutic Potential ◽  
Marker Gene ◽  
Orthodontic Tooth Movement ◽  
High Mobility ◽  
High Mobility Group ◽  
Nodule Formation ◽  
Hmgb1 Protein ◽  
Pdl Cells

High mobility group box protein-1 (HMGB1) is mainly recognized as a chemoattractant for macrophages in the initial phase of host response to pathogenic stimuli. However, recent findings provide evidence for anabolic properties in terms of enhanced proliferation, migration, and support of wound healing capacity of mesenchymal cells suggesting a dual role of the cytokine in the regulation of immune response and subsequent regenerative processes. Here, we examined potential anabolic effects of HMGB1 on human periodontal ligament (PDL) cells in the regulation of periodontal remodelling, for example, during orthodontic tooth movement. Preconfluent human PDL cells (hPDL) were exposed to HMGB1 protein and the influence on proliferation, migration, osteogenic differentiation, and biomineralization was determined by MTS assay, real time PCR, immunofluorescence cytochemistry, ELISA, and von Kossa staining. HMGB1 protein increased hPDL cell proliferation, migration, osteoblastic marker gene expression, and protein production as well as mineralized nodule formation significantly. The present findings support the dual character of HMGB1 with anabolic therapeutic potential that might support the reestablishment of the structural and functional integrity of the periodontium following periodontal trauma such as orthodontic tooth movement.

scholarly journals Mechanosensitive Piezo1 in Periodontal Ligament Cells Promotes Alveolar Bone Remodeling During Orthodontic Tooth Movement

2021 ◽  
Vol 12 ◽  
Author(s):  
Yukun Jiang ◽  
Yuzhe Guan ◽  
Yuanchen Lan ◽  
Shuo Chen ◽  
Tiancheng Li ◽  
...  
Keyword(s):  
Bone Remodeling ◽  
Periodontal Ligament ◽  
Alveolar Bone ◽  
Tooth Movement ◽  
Critical Role ◽  
Orthodontic Tooth Movement ◽  
Chemical Signals ◽  
Periodontal Tissues ◽  
Alveolar Bone Remodeling ◽  
Pdl Cells

Orthodontic tooth movement (OTM) is a process depending on the remodeling of periodontal tissues surrounding the roots. Orthodontic forces trigger the conversion of mechanical stimuli into intercellular chemical signals within periodontal ligament (PDL) cells, activating alveolar bone remodeling, and thereby, initiating OTM. Recently, the mechanosensitive ion channel Piezo1 has been found to play pivotal roles in the different types of human cells by transforming external physical stimuli into intercellular chemical signals. However, the function of Piezo1 during the mechanotransduction process of PDL cells has rarely been reported. Herein, we established a rat OTM model to study the potential role of Piezo1 during the mechanotransduction process of PDL cells and investigate its effects on the tension side of alveolar bone remodeling. A total of 60 male Sprague-Dawley rats were randomly assigned into three groups: the OTM + inhibitor (INH) group, the OTM group, and the control (CON) group. Nickel-titanium orthodontic springs were applied to trigger tooth movement. Mice were sacrificed on days 0, 3, 7, and 14 after orthodontic movement for the radiographic, histological, immunohistochemical, and molecular biological analyses. Our results revealed that the Piezo1 channel was activated by orthodontic force and mainly expressed in the PDL cells during the whole tooth movement period. The activation of the Piezo1 channel was essential for maintaining the rate of orthodontic tooth movement and facilitation of new alveolar bone formation on the tension side. Reduced osteogenesis-associated transcription factors such as Runt-related transcription factor 2 (RUNX2), Osterix (OSX), and receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin (OPG) ratio were examined when the function of Piezo1 was inhibited. In summary, Piezo1 plays a critical role in mediating both the osteogenesis and osteoclastic activities on the tension side during OTM.

scholarly journals Biomechanical and biological responses of periodontium in orthodontic tooth movement: up-date in a new decade

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Yuan Li ◽  
Qi Zhan ◽  
Minyue Bao ◽  
Jianru Yi ◽  
Yu Li
Keyword(s):  
Communication Networks ◽  
Periodontal Ligament ◽  
Cell Activation ◽  
Tooth Movement ◽  
Root Resorption ◽  
Orthodontic Tooth Movement ◽  
Sterile Inflammation ◽  
Periodontal Ligament Cells ◽  
Mechanical Stimuli ◽  
Biological Responses

AbstractNowadays, orthodontic treatment has become increasingly popular. However, the biological mechanisms of orthodontic tooth movement (OTM) have not been fully elucidated. We were aiming to summarize the evidences regarding the mechanisms of OTM. Firstly, we introduced the research models as a basis for further discussion of mechanisms. Secondly, we proposed a new hypothesis regarding the primary roles of periodontal ligament cells (PDLCs) and osteocytes involved in OTM mechanisms and summarized the biomechanical and biological responses of the periodontium in OTM through four steps, basically in OTM temporal sequences, as follows: (1) Extracellular mechanobiology of periodontium: biological, mechanical, and material changes of acellular components in periodontium under orthodontic forces were introduced. (2) Cell strain: the sensing, transduction, and regulation of mechanical stimuli in PDLCs and osteocytes. (3) Cell activation and differentiation: the activation and differentiation mechanisms of osteoblast and osteoclast, the force-induced sterile inflammation, and the communication networks consisting of sensors and effectors. (4) Tissue remodeling: the remodeling of bone and periodontal ligament (PDL) in the compression side and tension side responding to mechanical stimuli and root resorption. Lastly, we talked about the clinical implications of the updated OTM mechanisms, regarding optimal orthodontic force (OOF), acceleration of OTM, and prevention of root resorption.

scholarly journals Effects of the Highly COX-2-Selective Analgesic NSAID Etoricoxib on Human Periodontal Ligament Fibroblasts during Compressive Orthodontic Mechanical Strain

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Christian Kirschneck ◽  
Erika Calvano Küchler ◽  
Michael Wolf ◽  
Gerrit Spanier ◽  
Peter Proff ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Periodontal Ligament ◽  
Tooth Movement ◽  
Compressive Strain ◽  
Mechanical Strain ◽  
Orthodontic Tooth Movement ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling ◽  
Periodontal Inflammation ◽  
Cox 2

Human periodontal ligament (hPDL) fibroblasts play a major role during periodontitis and orthodontic tooth movement, mediating periodontal inflammation, osteoclastogenesis, and collagen synthesis. The highly COX-2-selective NSAID etoricoxib has a favorable systemic side effect profile and high analgesic efficacy, particularly for orthodontic pain. In this in vitro study, we investigated possible side effects of two clinically relevant etoricoxib concentrations on the expression pattern of mechanically strained hPDL fibroblasts and associated osteoclastogenesis in a model of simulated orthodontic compressive strain occurring during orthodontic tooth movement. hPDL fibroblasts were incubated for 72 h under physiological conditions with etoricoxib at 0 μM, 3.29 μM, and 5.49 μM, corresponding to clinically normal and subtoxic dosages, with and without mechanical strain by compression (2 g/cm2) for the final 48 h, simulating conditions during orthodontic tooth movement in compressive areas of the periodontal ligament. We then determined gene and/or protein expression of COX-2, IL-6, PG-E2, RANK-L, OPG, ALPL, VEGF-A, P4HA1, COL1A2, and FN1 via RT-qPCR, ELISA, and Western blot analyses as well as apoptosis, necrosis, cell viability, and cytotoxicity via FACS, MTT, and LDH assays. In addition, hPDL fibroblast-mediated osteoclastogenesis was assessed by TRAP staining in coculture with RAW267.4 cells for another 72 h. Gene and protein expression of all evaluated factors was significantly induced by the mechanical compressive strain applied. Etoricoxib at 3.29 μM and 5.49 μM significantly inhibited PG-E2 synthesis, but not COX-2 and IL-6 gene expression nor RANK-L-/OPG-mediated osteoclastogenesis or angiogenesis (VEGF-A). Extracellular matrix remodeling (COL1A2, FN1) and bone anabolism (ALPL), by contrast, were significantly stimulated particularly at 5.49 μM. In general, no adverse etoricoxib effects on hPDL fibroblasts regarding apoptosis, necrosis, cell viability, or cytotoxicity were detected. Clinically dosed etoricoxib, that is, a highly selective COX-2 inhibition, did not have substantial effects on hPDL fibroblast-mediated periodontal inflammation, extracellular matrix remodeling, RANK-L/OPG expression, and osteoclastogenesis during simulated orthodontic compressive strain.

Sign in / Sign up

Export Citation Format

Share Document