scholarly journals Growth Differentiation Factor 5 (GDF-5) Induces Matrix Metalloproteinase 2 (MMP-2) Expression in Periodontal Ligament Cells and Modulates MMP-2 and MMP-13 Activity in Osteoblasts

2010 ◽  
Vol 3 ◽  
pp. BTRI.S8120 ◽  
Author(s):  
Yuji Hatakeyama ◽  
Junko Hatakeyama ◽  
Yuriko Maruya ◽  
Kyoko Oka ◽  
Eichi Tsuruga ◽  
...  
Keyword(s):  
Gene Expression ◽  
Map Kinase ◽  
Periodontal Ligament ◽  
P38 Map Kinase ◽  
Matrix Metalloproteinase 2 ◽  
Type I ◽  
Periodontal Tissues ◽  
Differentiation Factor ◽  
Pdl Cells ◽  
Growth Differentiation Factor 5

Growth differentiation factor 5 (GDF-5), a member of the transforming growth factor beta (TGF-β) superfamily expressed in periodontal tissues, promotes extracellular matrix (ECM) in periodontal ligament (PDL) cells. Matrix metalloproteinases (MMP) are proteolytic enzymes that degrade ECM and are expressed in PDL cells. To date, little is known about the regulation of MMP synthesis and secretion in PDL cells. The aim of this study is to examine the effects of GDF-5 on MMP production and activity in PDL cells. GDF-5 increased both collagen type I alpha 2 (Col Iα2) and MMP-2 gene expression in cells derived from mouse PDL tissues after 3 days of culture. Because PDL cells represent a heterogeneous population, we examined gelatinolytic activity and gene expression profiles in an osteoblast cell line. After 6, 12, 24, and 48 hours of culture, GDF-5 increased both Col Iα2 and MMP gene expression in osteoblasts. GDF-5 also promoted MMP-2 activity as revealed by gelatin zymography after 7 days of culture. In the presence of the p38 MAP kinase inhibitor SB202190, on the other hand, MMP-2 activity was blocked. Taken together, these results indicate that GDF-5 may increase simultaneously the gene expression of type I collagen and MMP-2 in the osteoblast-like cells among the PDL cells and p38 MAP kinase pathway in osteoblast could involve in the regulation of MMP-2 enzyme activity induced by GDF-5.

scholarly journals Autophagy facilitates type I collagen synthesis in periodontal ligament cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tomomi Nakamura ◽  
Motozo Yamashita ◽  
Kuniko Ikegami ◽  
Mio Suzuki ◽  
Manabu Yanagita ◽  
...  
Keyword(s):  
Periodontal Ligament ◽  
Collagen Synthesis ◽  
Type I Collagen ◽  
Periodontal Diseases ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Physiological Role ◽  
Type I ◽  
Periodontal Tissue ◽  
Pdl Cells

AbstractAutophagy is a lysosomal protein degradation system in which the cell self-digests its intracellular protein components and organelles. Defects in autophagy contribute to the pathogenesis of age-related chronic diseases, such as myocardial infarction and rheumatoid arthritis, through defects in the extracellular matrix (ECM). However, little is known about autophagy in periodontal diseases characterised by the breakdown of periodontal tissue. Tooth-supportive periodontal ligament (PDL) tissue contains PDL cells that produce various ECM proteins such as collagen to maintain homeostasis in periodontal tissue. In this study, we aimed to clarify the physiological role of autophagy in periodontal tissue. We found that autophagy regulated type I collagen synthesis by elimination of misfolded proteins in human PDL (HPDL) cells. Inhibition of autophagy by E-64d and pepstatin A (PSA) or siATG5 treatment suppressed collagen production in HPDL cells at mRNA and protein levels. Immunoelectron microscopy revealed collagen fragments in autolysosomes. Accumulation of misfolded collagen in HPDL cells was confirmed by sodium dodecyl sulfate–polyacrylamide gel electrophoresis. E-64d and PSA treatment suppressed and rapamycin treatment accelerated the hard tissue-forming ability of HPDL cells. Our findings suggest that autophagy is a crucial regulatory process that facilitates type I collagen synthesis and partly regulates osteoblastic differentiation of PDL cells.

TNF-α and serum induce SKALP/elafin gene expression in human keratinocytes by a p38 MAP kinase-dependent pathway

2000 ◽  
Vol 292 (4) ◽  
pp. 180-187 ◽  
Author(s):  
R. Pfundt ◽  
M. Wingens ◽  
M. Bergers ◽  
M. Zweers ◽  
M. Frenken ◽  
...  
Keyword(s):  
Gene Expression ◽  
Map Kinase ◽  
Human Keratinocytes ◽  
P38 Map Kinase ◽  
Tnf Α ◽  
Dependent Pathway

scholarly journals Differential role of cAMP, cGMP and Ca2+ and involvement of kinases and CBP-CREB-CRE pathway in regulation of arylalkylamine N-acetyltransferase 2 gene in the pineal organ of air-breathing catfish, Clarias gariepinus

2021 ◽  
Author(s):  
Hijam Nonibala ◽  
Braj Bansh Prasad Gupta
Keyword(s):  
Gene Expression ◽  
Map Kinase ◽  
Gene Transcription ◽  
Pineal Organ ◽  
Clarias Gariepinus ◽  
Specific Inhibitor ◽  
P38 Map Kinase ◽  
Camp And Cgmp

Abstract Transcription of arylalkylamine N-acetyltransferase 2 (aanat2) gene leads to formation of AANAT2 - the rate-limiting enzyme in melatonin synthesis pathway in photosensitive fish pineal organ. However, unlike in avian and mammalian pineal gland, there is practically no information on signal transduction pathway(s) involved in regulation of aanat2 gene transcription in the fish pineal organ. Therefore, we investigated the role of important molecular components of signalling via cAMP, cGMP, Ca2+ involving PKA, PKG, PKC, MeK and p38 MAP kinase as well as possible role of serine/threonine phosphatases, CREB and CBP using their specific inhibitors and/or activators in aanat2 gene transcription in the fish pineal organ maintained under in vitro culture-conditions. db-cAMP and db-cGMP stimulated the expression of aanat2 gene. db-cAMP- and cGMP-induced aanat2 gene expression was significantly reduced in the presence of H-89 (specific inhibitor of PKA), KT5823 (specific inhibitor of PKG), chelerythrine chloride (specific inhibitor of PKC), U0126 ethanolate (specific inhibitor of MeK) and SB 202190 monohydrochloride hydrate (specific inhibitor of p38 MAP kinase). Inhibitors of PP1 and PP2A significantly increased aanat2 gene expression as well as significantly reduced cAMP- and cGMP-induced gene transcription, while inhibitor of PP2B had no effect on aanat2 gene expression. Inhibitors of both CREB and CBP-CREB interaction completely blocked cAMP-induced aanat2 gene transcription. Based on these findings, we suggest that cAMP, cGMP and Ca2+ stimulate aanat2 gene transcription via PKA, PKG and PKC, respectively. Further, protein phosphatases and CBP-CREB-CRE pathway are actively involved in regulation of on aanat2 gene expression in the fish pineal organ.

scholarly journals Identification of Type I and Type II Serine/Threonine Kinase Receptors for Growth/Differentiation Factor-5

1996 ◽  
Vol 271 (35) ◽  
pp. 21345-21352 ◽  
Author(s):  
Hideki Nishitoh ◽  
Hidenori Ichijo ◽  
Michio Kimura ◽  
Tomoaki Matsumoto ◽  
Fusao Makishima ◽  
...  
Keyword(s):  
Type I ◽  
Type Ii ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Differentiation Factor ◽  
Growth Differentiation Factor 5

scholarly journals LPS fromP. gingivalisand Hypoxia Increases Oxidative Stress in Periodontal Ligament Fibroblasts and Contributes to Periodontitis

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
L. Gölz ◽  
S. Memmert ◽  
B. Rath-Deschner ◽  
A. Jäger ◽  
T. Appel ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Periodontal Ligament ◽  
Inflammatory Diseases ◽  
Periodontal Pathogen ◽  
Oral Diseases ◽  
Redox Systems ◽  
Periodontal Ligament Fibroblasts ◽  
Prolonged Incubation ◽  
Periodontal Tissues ◽  
Pdl Cells

Oxidative stress is characterized by an accumulation of reactive oxygen species (ROS) and plays a key role in the progression of inflammatory diseases. We hypothesize that hypoxic and inflammatory events induce oxidative stress in the periodontal ligament (PDL) by activating NOX4. Human primary PDL fibroblasts were stimulated with lipopolysaccharide fromPorphyromonas gingivalis(LPS-PG), a periodontal pathogen bacterium under normoxic and hypoxic conditions. By quantitative PCR, immunoblot, immunostaining, and a specific ROS assay we determined the amount of NOX4, ROS, and several redox systems. Healthy and inflamed periodontal tissues were collected to evaluate NOX4 and redox systems by immunohistochemistry. We found significantly increased NOX4 levels after hypoxic or inflammatory stimulation in PDL cells (P<0.001) which was even more pronounced after combination of the stimuli. This was accompanied by a significant upregulation of ROS and catalase (P<0.001). However, prolonged incubation with both stimuli induced a reduction of catalase indicating a collapse of the protective machinery favoring ROS increase and the progression of inflammatory oral diseases. Analysis of inflamed tissues confirmed our hypothesis. In conclusion, we demonstrated that the interplay of NOX4 and redox systems is crucial for ROS formation which plays a pivotal role during oral diseases.

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 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.

Activation of Nrf2/ARE pathway protects endothelial cells from oxidant injury and inhibits inflammatory gene expression

2006 ◽  
Vol 290 (5) ◽  
pp. H1862-H1870 ◽  
Author(s):  
Xi-Lin Chen ◽  
Geraldine Dodd ◽  
Suzanne Thomas ◽  
Xiaolan Zhang ◽  
Martin A. Wasserman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Map Kinase ◽  
P38 Map Kinase ◽  
Control Element ◽  
Related Factor ◽  
Dependent Manner ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene ◽  
Tnf Α

The antioxidant response element (ARE) is a transcriptional control element that mediates expression of a set of antioxidant proteins. NF-E2-related factor 2 (Nrf2) is a transcription factor that activates ARE-containing genes. In endothelial cells, the ARE-mediated genes are upregulated by atheroprotective laminar flow through a Nrf2-dependent mechanism. We tested the hypothesis that activation of ARE-regulated genes via adenovirus-mediated expression of Nrf2 may suppress redox-sensitive inflammatory gene expression. Expression of Nrf2 in human aortic endothelial cells (HAECs) resulted in a marked increase in ARE-driven transcriptional activity and protected HAECs from H2O2-mediated cytotoxicity. Nrf2 suppressed TNF-α-induced monocyte chemoattractant protein (MCP)-1 and VCAM-1 mRNA and protein expression in a dose-dependent manner and inhibited TNF-α-induced monocytic U937 cell adhesion to HAECs. Nrf2 also inhibited IL-1β-induced MCP-1 gene expression in human mesangial cells. Expression of Nrf2 inhibited TNF-α-induced activation of p38 MAP kinase. Furthermore, expression of a constitutively active form of MKK6 (an upstream kinase for p38 MAP kinase) partially reversed Nrf2-mediated inhibition of VCAM-1 expression, suggesting that p38 MAP kinase, at least in part, mediates Nrf2's anti-inflammatory action. In contrast, Nrf2 did not inhibit TNF-α-induced NF-κB activation. These data identify the Nrf2/ARE pathway as an endogenous atheroprotective system for antioxidant protection and suppression of redox-sensitive inflammatory genes, suggesting that targeting the Nrf2/ARE pathway may represent a novel therapeutic approach for the treatment of inflammatory diseases such as atherosclerosis.

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