PTHrP Induces Notch Signaling in Periodontal Ligament Cells

2009 ◽  
Vol 88 (6) ◽  
pp. 551-556 ◽  
Author(s):  
A. Nakao ◽  
H. Kajiya ◽  
H. Fukushima ◽  
A. Fukushima ◽  
H. Anan ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Notch Signaling ◽  
Periodontal Ligament ◽  
Alveolar Bone ◽  
Root Resorption ◽  
Tooth Eruption ◽  
Periodontal Ligament Cells ◽  
Dependent Manner ◽  
Human Pdl Cells ◽  
Pdl Cells

Periodontal ligament (PDL) cells are known to play important roles in tooth eruption and alveolar bone metabolism. We previously reported that PTHrP increases RANKL expression in human PDL cells, suggesting that it promotes odontoclastic root resorption during tooth eruption. While it is known that Notch-related genes play a key role during bone development, the role of the Notch signaling pathway in PDL cells during tooth and bone resorption is less clear. We hypothesized that PTHrP induces a Notch ligand in PDL cells and thereby regulates osteo- and odontoclastogenesis. We found that PTHrP increased Notch1 ligand Jagged1 expression in human PDL cells in a dose- and time-dependent manner. PTHrP-induced Jagged1 up-regulation was mediated by PKA activation, but not by PKC. Jagged1 also promoted RANKL-induced osteoclastogenesis. These results demonstrate that PTHrP induces Jagged1 expression in PDL cells, leading to osteo- and odontoclastogenesis, and thus likely promoting tooth and alveolar bone resorption.

Osteogenic Gene Expression by Human Periodontal Ligament Cells under Cyclic Tension

2007 ◽  
Vol 86 (12) ◽  
pp. 1212-1216 ◽  
Author(s):  
D.C. Wescott ◽  
M.N. Pinkerton ◽  
B.J. Gaffey ◽  
K.T. Beggs ◽  
T.J. Milne ◽  
...  
Keyword(s):  
Periodontal Ligament ◽  
Alveolar Bone ◽  
Mechanical Strain ◽  
Osteogenic Potential ◽  
Periodontal Ligament Cells ◽  
Orthodontic Appliances ◽  
Fiber Types ◽  
Pdl Cells ◽  
Array Technology ◽  
Osteogenic Gene Expression

The forces that orthodontic appliances apply to the teeth are transmitted through the periodontal ligament (PDL) to the supporting alveolar bone, leading to the deposition or resorption of bone, depending upon whether the tissues are exposed to a tensile or compressive mechanical strain. To evaluate the osteogenic potential of PDL cells, we applied a 12% uni-axial cyclic tensile strain to cultured human PDL cells and analyzed the differential expression of 78 genes implicated in osteoblast differentiation and bone metabolism by real-time RT-PCR array technology. Sixteen genes showed statistically significant changes in expression in response to alterations in their mechanical environment, including cell adhesion molecules and collagen fiber types. Genes linked to the osteoblast phenotype that were up-regulated included BMP2, BMP6, ALP, SOX9, MSX1, and VEGFA; those down-regulated included BMP4 and EGF. This study has expanded our knowledge of the transcriptional profile of PDL cells and identified several new mechanoresponsive genes.

Sphingomyelin Phosphodiesterase 3 Enhances Cytodifferentiation of Periodontal Ligament Cells

2016 ◽  
Vol 96 (3) ◽  
pp. 339-346 ◽  
Author(s):  
S. Miyauchi ◽  
J. Kitagaki ◽  
R. Masumoto ◽  
A. Imai ◽  
K. Kobayashi ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Periodontal Ligament ◽  
Type I Collagen ◽  
Alveolar Bone ◽  
Skeletal Development ◽  
Aggressive Periodontitis ◽  
Periodontal Ligament Cells ◽  
Type I ◽  
Phosphodiesterase 3 ◽  
Pdl Cells

Sphingomyelin phosphodiesterase 3 ( Smpd3), which encodes neutral sphingomyelinase 2 (nSMase2), is a key molecule for skeletal development as well as for the cytodifferentiation of odontoblasts and alveolar bone. However, the effects of nSMase2 on the cytodifferentiation of periodontal ligament (PDL) cells are still unclear. In this study, the authors analyzed the effects of Smpd3 on the cytodifferentiation of human PDL (HPDL) cells. The authors found that Smpd3 increases the mRNA expression of calcification-related genes, such as alkaline phosphatase (ALPase), type I collagen, osteopontin, Osterix (Osx), and runt-related transcription factor (Runx)-2 in HPDL cells. In contrast, GW4869, an inhibitor of nSMase2, clearly decreased the mRNA expression of ALPase, type I collagen, and osteocalcin in HPDL cells, suggesting that Smpd3 enhances HPDL cytodifferentiation. Next, the authors used exome sequencing to evaluate the genetic variants of Smpd3 in a Japanese population with aggressive periodontitis (AgP). Among 44 unrelated subjects, the authors identified a single nucleotide polymorphism (SNP), rs145616324, in Smpd3 as a putative genetic variant for AgP among Japanese people. Moreover, Smpd3 harboring this SNP did not increase the sphingomyelinase activity or mRNA expression of ALPase, type I collagen, osteopontin, Osx, or Runx2, suggesting that this SNP inhibits Smpd3 such that it has no effect on the cytodifferentiation of HPDL cells. These data suggest that Smpd3 plays a crucial role in maintaining the homeostasis of PDL tissue.

scholarly journals Porphyromonas gingivalis GroEL Induces Osteoclastogenesis of Periodontal Ligament Cells and Enhances Alveolar Bone Resorption in Rats

PLoS ONE ◽  
2014 ◽  
Vol 9 (7) ◽  
pp. e102450 ◽  
Author(s):  
Feng-Yen Lin ◽  
Fung-Ping Hsiao ◽  
Chun-Yao Huang ◽  
Chun-Ming Shih ◽  
Nai-Wen Tsao ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Porphyromonas Gingivalis ◽  
Periodontal Ligament ◽  
Alveolar Bone ◽  
Periodontal Ligament Cells

scholarly journals Ginsenoside Rb3 Inhibits Pro-Inflammatory Cytokines via MAPK/AKT/NF-κB Pathways and Attenuates Rat Alveolar Bone Resorption in Response to Porphyromonas gingivalis LPS

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4815
Author(s):  
Minmin Sun ◽  
Yaoting Ji ◽  
Zhen Li ◽  
Rourong Chen ◽  
Shuhui Zhou ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Porphyromonas Gingivalis ◽  
Alveolar Bone ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Periodontal Ligament Cells ◽  
Dependent Manner ◽  
Experimental Periodontitis ◽  
Anti Inflammatory ◽  
Porphyromonas Gingivalis Lps

Conventional treatments for chronic periodontitis are less effective in controlling inflammation and often relapse. Therefore, it is necessary to explore an immunomodulatory medication as an adjuvant. Ginsenoside Rb3 (Rb3), one of the most abundant active components of ginseng, has been found to possess anti-inflammatory and immunomodulatory properties. Here, we detected the anti-inflammatory effect of Rb3 on Porphyromonas gingivalis LPS-stimulated human periodontal ligament cells and experimental periodontitis rats for the first time. We found that the expression of pro-inflammatory mediators, including IL-1β, IL-6 and IL-8, upregulated by lipopolysaccharide (LPS) stimulation was remarkably downregulated by Rb3 treatment in a dose-dependent manner at both transcriptional and translational levels. Network pharmacological analysis of Rb3 showed that the mitogen-activated protein kinase (MAPK) signaling pathway had the highest richness and that p38, JNK, and ERK molecules were potential targets of Rb3 in humans. Western blot analysis revealed that Rb3 significantly suppressed the phosphorylation of p38 MAPK and p65 NF-κB, as well as decreased the expression of total AKT. In experimental periodontitis rat models, reductions in alveolar bone resorption and osteoclast generation were observed in the Rb3 treatment group. Thus, we can conclude that Rb3 ameliorated Porphyromonas gingivalis LPS-induced inflammation by inhibiting the MAPK/AKT/NF-κB signaling pathways and attenuated alveolar bone resorption in experimental periodontitis rats.

Nicotine-upregulated miR-30a arrests cell cycle in G1 phase by directly targeting CCNE2 in human periodontal ligament cells

2020 ◽  
Vol 98 (3) ◽  
pp. 354-361
Author(s):  
Lizheng Wu ◽  
Kuan Yang ◽  
Yajie Gui ◽  
Xiaojing Wang
Keyword(s):  
Cell Cycle ◽  
Periodontal Ligament ◽  
Luciferase Reporter ◽  
Pcr Analysis ◽  
Periodontal Ligament Cells ◽  
Periodontal Tissues ◽  
Human Pdl Cells ◽  
Pdl Cells ◽  
Reporter Assays

The consumption of nicotine via smoking tobacco has been reported to stimulate the occurrence and progression of periodontitis. Many studies have demonstrated that nicotine prevents the regeneration of periodontal tissues primarily by inhibiting the proliferation of human periodontal ligament (PDL) cells. However, the mechanisms underlying this process are still unclear. Therefore, we investigated whether nicotine-upregulated miR-30a inhibited the proliferation of human PDL cells by downregulating cyclin E2 (CCNE2), in vitro. Quantitative real-time PCR analysis revealed that nicotine upregulated the expression of miR-30a in human PDL cells. In addition, nicotine inhibited the proliferation of human PDL cells by inducing cell cycle arrest. To support this hypothesis, we showed that nicotine downregulated the expression of CCNE2 in human PDL cells, whereas inhibition of miR-30a restored CCNE2 expression that had been downregulated by nicotine. Furthermore, using luciferase reporter assays, we found that miR-30a directly interacts with the CCNE2 3′UTR. In conclusion, these findings indicate that nicotine-upregulated miR-30a inhibits the proliferation of human PDL cells by downregulating the expression of CCNE2.

Cyclical Tensile Force on Periodontal Ligament Cells Inhibits Osteoclastogenesis through OPG Induction

2006 ◽  
Vol 85 (5) ◽  
pp. 457-462 ◽  
Author(s):  
H. Kanzaki ◽  
M. Chiba ◽  
A. Sato ◽  
A. Miyagawa ◽  
K. Arai ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Periodontal Ligament ◽  
Neutralizing Antibodies ◽  
Tensile Force ◽  
Compressive Force ◽  
Conditioned Media ◽  
Periodontal Ligament Cells ◽  
Dependent Manner ◽  
Tgf Beta ◽  
Pdl Cells

The periodontal ligament (PDL) maintains homeostasis of periodontal tissue under mechanical tensile-loading caused by mastication. Occlusal load inhibits atrophic alveolar bone resorption. Previously, we discovered that continuous compressive force on PDL cells induced osteoclastogenesis-supporting activity, with up-regulation of RANKL. We hypothesized that, unlike compression, cyclical tensile force up-regulates OPG expression in PDL cells via TGF-beta up-regulation, and does not induce osteoclastogenesis-supporting activity. PDL cells were mechanically stimulated by cyclical tensile force in vitro. The conditioned media of PDL cells that had been subjected to cyclical tensile force inhibited osteoclastogenesis. Cyclical tensile force up-regulated not only RANKL mRNA expression, but also OPG mRNA expression in PDL cells. Tensile force up-regulated TGF-beta expression in PDL cells as well. Administration of neutralizing antibodies to TGF-beta inhibited OPG up-regulation under cyclical tensile-force stimulation in a dose-dependent manner. Additionally, the osteoclastogenesis-inhibitory effect of the conditioned media of PDL cells under cyclical tensile force was partially rescued by the administration of TGF-beta neutralizing antibodies. In conclusion, tensile force inhibited the osteoclastogenesis-supporting activity of PDL cells by inducing the up-regulation of OPG via TGF-beta stimulation.

RANKL Increase in Compressed Periodontal Ligament Cells from Root Resorption

2006 ◽  
Vol 85 (8) ◽  
pp. 751-756 ◽  
Author(s):  
M. Yamaguchi ◽  
N. Aihara ◽  
T. Kojima ◽  
K. Kasai
Keyword(s):  
Periodontal Ligament ◽  
Root Resorption ◽  
Compressive Force ◽  
Osteoclast Formation ◽  
Periodontal Ligament Cells ◽  
Apical Root Resorption ◽  
Pdl Cells ◽  
Receptor Activator ◽  
External Apical Root Resorption ◽  
The Relationship

The ligand receptor activator of NFκB (RANKL) plays an important role in osteoclast formation. However, very little is known about the relationship between external apical root resorption during orthodontic treatment and RANKL. We hypothesized that compressive force is responsible for RANKL formation and up-regulation of osteoclastogenesis in periodontal ligament (PDL) cells from patients with severe orthodontically induced external apical root resorption. RANKL and osteoprotegerin (OPG) production, TRAP-positive cells, and resorptive pits were determined. The increase of RANKL and the decrease of OPG were greater in the severe root resorption group than in the non-resorption group. The numbers of TRAP-positive cells and resorptive pits were also increased in the severe root resorption group than in the non-resorption group. These results support the hypothesis that the compressed PDL cells obtained from tissues with severe external apical root resorption may produce a large amount of RANKL and up-regulate osteoclastogenesis.

Expression of MMP-8 and MMP-13 mRNAs in Rat Periodontium during Tooth Eruption

2002 ◽  
Vol 81 (10) ◽  
pp. 673-678 ◽  
Author(s):  
M. Tsubota ◽  
Y. Sasano ◽  
I. Takahashi ◽  
M. Kagayama ◽  
H. Shimauchi
Keyword(s):  
Periodontal Ligament ◽  
Alveolar Bone ◽  
Small Population ◽  
Tooth Eruption ◽  
Periodontal Ligament Cells ◽  
Rt Pcr ◽  
Collagen Types ◽  
Paraffin Sections ◽  
Periodontal Tissues

The present study was designed to investigate mRNA expression of matrix metalloproteinase-8 (MMP-8) and MMP-13 in forming periodontium during tooth eruption in the rat. RT-PCR for the decalcified paraffin sections indicated expression of MMP-8 and MMP-13 in the periodontal tissues. In situ hydridization demonstrated expression of MMP-8 in osteoblasts, osteocytes, periodontal ligament cells, cementoblasts, and cementocytes along with collagen types I and III. In contrast, transcripts of MMP-13 were confined to a small population of osteoblasts and osteocytes in alveolar bone. The results suggested that MMP-8 may be involved in remodeling the periodontium during tooth eruption, and its expression may be coordinated with that of collagen types I and III, whereas the participation of MMP-13 may be rather limited.

scholarly journals Force-induced Adrb2 in Periodontal Ligament Cells Promotes Tooth Movement

2014 ◽  
Vol 93 (11) ◽  
pp. 1163-1169 ◽  
Author(s):  
H. Cao ◽  
X. Kou ◽  
R. Yang ◽  
D. Liu ◽  
X. Wang ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Periodontal Ligament ◽  
Alveolar Bone ◽  
Tooth Movement ◽  
Osteoclast Differentiation ◽  
Compressive Force ◽  
Mechanical Force ◽  
Periodontal Ligament Cells ◽  
Force Application ◽  
Alveolar Bone Remodeling

The sympathetic nervous system (SNS) regulates bone resorption through β-2 adrenergic receptor (Adrb2). In orthodontic tooth movement (OTM), mechanical force induces and regulates alveolar bone remodeling. Compressive force-associated osteoclast differentiation and alveolar bone resorption are the rate-limiting steps of tooth movement. However, whether mechanical force can activate Adrb2 and thus contribute to OTM remains unknown. In this study, orthodontic nickel-titanium springs were applied to the upper first molars of rats and Adrb1/2-/- mice to confirm the role of SNS and Adrb2 in OTM. The results showed that blockage of SNS activity in the jawbones of rats by means of superior cervical ganglion ectomy reduced OTM distance from 860 to 540 μm after 14 d of force application. In addition, the injection of nonselective Adrb2 agonist isoproterenol activated the downstream signaling of SNS to accelerate OTM from 300 to 540 μm after 7 d of force application. Adrb1/2-/- mice showed significantly reduced OTM distance (19.5 μm) compared with the wild-type mice (107.6 μm) after 7 d of force application. Histopathologic analysis showed that the number of Adrb2-positive cells increased in the compressive region of periodontal ligament after orthodontic force was applied on rats. Mechanistically, mechanical compressive force upregulated Adrb2 expression in primary-cultured human periodontal ligament cells (PDLCs) through the elevation of intracellular Ca2+ concentration. Activation of Adrb2 in PDLCs increased the RANKL/OPG ratio and promoted the peripheral blood mononuclear cell differentiation to osteoclasts in the cocultured system. Upregulation of Adrb2 in PDLCs promoted osteoclastogenesis, which accelerated OTM through Adrb2-enhanced bone resorption. In summary, this study suggests that mechanical force-induced Adrb2 activation in PDLCs contributes to SNS-regulated OTM.

In vitro Cellular Aging Stimulates Interleukin-1β Production in Stretched Human Periodontal-ligament-derived Cells

1997 ◽  
Vol 76 (7) ◽  
pp. 1367-1375 ◽  
Author(s):  
N. Shimizu ◽  
T. Goseki ◽  
M. Yamaguchi ◽  
T. Iwasawa ◽  
H. Takiguchi ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Periodontal Disease ◽  
Mechanical Stress ◽  
Periodontal Ligament ◽  
Periodontal Diseases ◽  
Cellular Aging ◽  
Mechanical Tension ◽  
Human Pdl Cells ◽  
Pdl Cells

Although the severity of periodontal disease is known to be affected by host age, the pathological role of aging in periodontal disease, and especially that attributable to trauma from occlusion, has not been well-characterized. Interleukin (IL)-1β is a key mediator involved in periodontal diseases, a potent stimulator of bone resorption. Furthermore, it is produced by human periodontal ligament (PDL) cells in response to mechanical stress. To investigate the age-related changes in the biosynthetic capacity of IL-1β in PDL cells, we examined the effects of in vitro cellular aging with mechanical stress on IL-1β protein and gene expression by human PDL cells. Human PDL cells (young = 5th or 6th passage; old = 18-20th passage) were cultured on flexible-bottomed culture plates, and the cells were deformed at 6 cycles per min at 2 steps of tension force for 1 to 5 days. We found a two-fold increase in IL-lp production by old PDL cells subjected to mechanical tension compared with that by young PDL cells, although the constitutive levels of IL-1β were similar in both the young and old PDL cells. This increase was tension-dependent. IL-1β mRNA was also detected in both the cell types under basal conditions, and its expression was further enhanced by application of mechanical tension by use of reverse-transcription-polymerase chain-reaction (RT-PCR) and in situ hybridization methods. The increase in signal rate was higher in the old cells than in the young cells. IL-1β-converting enzyme mRNA remained unchanged. It is possible that a large amount of IL-1β produced by PDL cells from an aged host in response to mechanical force may be positively related to the accleration of alveolar bone resorption.

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