scholarly journals MAPK Usage in Periodontal Disease Progression

2012 ◽  
Vol 2012 ◽  
pp. 1-17 ◽  
Author(s):  
Qiyan Li ◽  
Michael S. Valerio ◽  
Keith L. Kirkwood
Keyword(s):  
Bone Loss ◽  
Periodontal Disease ◽  
Disease Progression ◽  
P38 Mapk ◽  
Rna Binding ◽  
Cytokine Expression ◽  
Negative Regulator ◽  
Host Recognition ◽  
Mapk Activation ◽  
Periodontal Inflammation

In periodontal disease, host recognition of bacterial constituents, including lipopolysaccharide (LPS), induces p38 MAPK activation and subsequent inflammatory cytokine expression, favoring osteoclastogenesis and increased net bone resorption in the local periodontal environment. In this paper, we discuss evidence that the p38/MAPK-activated protein kinase-2 (MK2) signaling axis is needed for periodontal disease progression: an orally administered p38α inhibitor reduced the progression of experimental periodontal bone loss by reducing inflammation and cytokine expression. Subsequently, the significance of p38 signaling was confirmed with RNA interference to attenuate MK2-reduced cytokine expression and LPS-induced alveolar bone loss. MAPK phosphatase-1 (MKP-1), a negative regulator of MAPK activation, was also critical for periodontal disease progression. In MPK-1-deficient mice, p38-sustained activation increased osteoclast formation and bone loss, whereas MKP-1 overexpression dampened p38 signaling and subsequent cytokine expression. Finally, overexpression of the p38/MK2 target RNA-binding tristetraprolin (TTP) decreased mRNA stability of key inflammatory cytokines at the posttranscriptional level, thereby protecting against periodontal inflammation. Collectively, these studies highlight the importance of p38 MAPK signaling in immune cytokine production and periodontal disease progression.

scholarly journals Nicorandil Inhibits Osteoclast Formation Base on NF-κB and p-38 MAPK Signaling Pathways and Relieves Ovariectomy-Induced Bone Loss

2021 ◽  
Vol 12 ◽  
Author(s):  
Shenggui Xu ◽  
Xiankun Cao ◽  
Zhenxing Yu ◽  
Wenxin He ◽  
Yichuan Pang ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Signaling Pathways ◽  
P38 Mapk ◽  
Biological Effects ◽  
Mapk Signaling ◽  
Osteoclast Formation ◽  
Mineral Density ◽  
Mapk Activation ◽  
Bone Disorders

Osteolytic bone disorders are characterized by an overall reduction in bone mineral density which enhances bone ductility and vulnerability to fractures. This disorder is primarily associated with superabundant osteoclast formation and bone resorption activity. Nicorandil (NIC) is a vasodilatory anti-anginal drug with ATP-dependent potassium (KATP) channel openings. However, NIC is adopted to manage adverse cardiovascular and coronary events. Recent research has demonstrated that NIC also possesses anti-inflammatory peculiarity through the regulation of p38 MAPK and NF-κB signaling pathways. Both MAPK and NF-κB signaling pathways play pivotal roles in RANKL-induced osteoclast formation and bone resorption function. Herein, we hypothesized that NIC may exert potential biological effects against osteoclasts, and revealed that NIC dose-dependently suppressed bone marrow macrophage (BMM) precursors to differentiate into TRAP + multinucleated osteoclasts in vitro. Furthermore, osteoclast resorption assays demonstrated anti-resorptive effects exhibited by NIC. NIC had no impact on osteoblast differentiation or mineralization function. Based on Biochemical analyses, NIC relieved RANKL-induced ERK, NF-κB and p38 MAPK signaling without noticeable effects on JNK MAPK activation. However, the attenuation of NF-κB and p38 MAPK activation was sufficient to hamper the downstream induction of c-Fos and NFATc1 expression. Meanwhile, NIC administration markedly protected mice from ovariectomy (OVX)-induced bone loss through in vivo inhibition of osteoclast formation and bone resorption activity. Collectively, this work demonstrated the potential of NIC in the management of osteolytic bone disorders mediated by osteoclasts.

scholarly journals Toll-Like Receptor Signaling and Immune Regulatory Lymphocytes in Periodontal Disease

2020 ◽  
Vol 21 (9) ◽  
pp. 3329 ◽  
Author(s):  
Yingzhi Gu ◽  
Xiaozhe Han
Keyword(s):  
Immune Response ◽  
B Cells ◽  
Bone Loss ◽  
Periodontal Disease ◽  
B Lymphocytes ◽  
Inflammatory Responses ◽  
Tlr Signaling ◽  
Periodontal Inflammation ◽  
Regulatory Lymphocytes

Periodontitis is known to be initiated by periodontal microbiota derived from biofilm formation. The microbial dysbiotic changes in the biofilm trigger the host immune and inflammatory responses that can be both beneficial for the protection of the host from infection, and detrimental to the host, causing tissue destruction. During this process, recognition of Pathogen-Associated Molecular Patterns (PAMPs) by the host Pattern Recognition Receptors (PRRs) such as Toll-like receptors (TLRs) play an essential role in the host–microbe interaction and the subsequent innate as well as adaptive responses. If persistent, the adverse interaction triggered by the host immune response to the microorganisms associated with periodontal biofilms is a direct cause of periodontal inflammation and bone loss. A large number of T and B lymphocytes are infiltrated in the diseased gingival tissues, which can secrete inflammatory mediators and activate the osteolytic pathways, promoting periodontal inflammation and bone resorption. On the other hand, there is evidence showing that immune regulatory T and B cells are present in the diseased tissue and can be induced for the enhancement of their anti-inflammatory effects. Changes and distribution of the T/B lymphocytes phenotype seem to be a key determinant of the periodontal disease outcome, as the functional activities of these cells not only shape up the overall immune response pattern, but may directly regulate the osteoimmunological balance. Therefore, interventional strategies targeting TLR signaling and immune regulatory T/B cells may be a promising approach to rebalance the immune response and alleviate bone loss in periodontal disease. In this review, we will examine the etiological role of TLR signaling and immune cell osteoclastogenic activity in the pathogenesis of periodontitis. More importantly, the protective effects of immune regulatory lymphocytes, particularly the activation and functional role of IL-10 expressing regulatory B cells, will be discussed.

scholarly journals The RNA-Binding Protein KSRP Modulates Cytokine Expression of CD4+ T Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Rudolf Käfer ◽  
Lisa Schmidtke ◽  
Katharina Schrick ◽  
Evelyn Montermann ◽  
Matthias Bros ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Cytokine Expression ◽  
Negative Regulator ◽  
Control Group ◽  
Type I

The KH-type splicing regulatory protein (KSRP) is a RNA-binding protein, which regulates the stability of many mRNAs encoding immune-relevant proteins. As KSRP regulates innate immune responses, for instance by the modulation of type I interferon mRNA stability, we were interested whether knockdown of the protein (KSRP-/-) interferes with T cell activation and polarization. Polyclonally stimulated KSRP-/- CD4+ T cells proliferated at a higher extent and higher frequency and expressed the activation marker CD25 more than wild-type T cells. In supernatants of stimulated KSRP-/- CD4+ T cells, levels of IL-5, IL-9, IL-10, and IL-13 were observed to be increased compared to those of the control group. KSRP-/- CD8+ T cells showed no altered proliferative capacity upon polyclonal stimulation, but supernatants contained lower levels of interferon-γ. Similar changes in the cytokine expression patterns were also detected in T cells derived from KSRP-/- mice undergoing arthritis induction indicative of a pathophysiological role of KSRP-dependent T cell polarization. We demonstrated the direct binding of KSRP to the 3′ untranslated region of IL-13, IL-10, and IFN-γ mRNA in in vitro experiments. Moreover, since IL-4 mRNA decay was reduced in KSRP-/- CD4+ T cells, we identify KSRP as a negative regulator of IL-4 expression. These data indicate that overexpression of IL-4, which constitutes the primary inducer of Th2 polarization, may cause the Th2 bias of polyclonally stimulated KSRP-/- CD4+ T cells. This is the first report demonstrating that KSRP is involved in the regulation of T cell responses. We present strong evidence that T cells derived from KSRP-/- mice favor Th2-driven immune responses.

Periodontal Health Status in a Colony of 109 Cats

2009 ◽  
Vol 26 (3) ◽  
pp. 147-155 ◽  
Author(s):  
Nicolas Girard ◽  
Eric Servet ◽  
Vincent Biourge ◽  
Philippe Hennet
Keyword(s):  
Bone Loss ◽  
Periodontal Disease ◽  
Aggressive Periodontitis ◽  
Tooth Surface ◽  
Healthy Population ◽  
Periodontal Inflammation ◽  
Wide Range ◽  
Periodontal Bone Loss

Periodontal disease has not been well characterized in the cat, and it is not known if feline tooth resorptions (TR) are equivalent to those observed in humans and dogs. The aim of this study was to investigate the different patterns of periodontal inflammation in cats, and to evaluate their prevalence in a standardized healthy population (n=109). Particular emphasis was placed on the potential associations between TR and periodontal parameters, as well as the influence of potential risk factors (including breed, sex, and age). A single complete periodontal examination was performed, including periodontal probing of each tooth and exploration of the tooth surface using a dental explorer; at least 10 radiographs were taken for each cat. Missing teeth with radiographic evidence of root apices were present in 34.0 % of cats. Periodontal disease was common, and 13.0 % of cats had aggressive periodontitis. All of the cats had some form of periodontal inflammation, and only 4.0 % of cats were free from gingival inflammation. Moderate to severe gingivitis was present in 13.0 % of teeth. Dental furcation exposure was present in 18.0 % of all multi-rooted teeth. Periodontal bone loss was observed in 31.2 % of teeth, with the majority (98.2 %) of all cats having some form of periodontal bone loss. Breed effects were identified for some variables. Eight of 14 periodontal variables were statistically correlated with Type 1 TR. Two of 14 variables (and age) were statistically correlated with Type 2 TR. In conclusion, the cats of this colony had a wide range of periodontal inflammation, including aggressive periodontitis. Type 1 TR and Type 2 TR were identified to be two significantly different manifestations of TR, with a strong association between Type 1 TR and periodontal disease.

scholarly journals Knockout of the KH-Type Splicing Regulatory Protein Drives Glomerulonephritis in MRL-Faslpr Mice

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3167
Author(s):  
Lisa Schmidtke ◽  
Myriam Meineck ◽  
Sabrina Saurin ◽  
Svenja Otten ◽  
Fabian Gather ◽  
...  
Keyword(s):  
T Cells ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Rna Binding ◽  
Regulatory Protein ◽  
Cytokine Expression ◽  
Negative Regulator ◽  
Transcriptional Level ◽  
Kidney Morphology ◽  
The Impact

KH-type splicing regulatory protein (KSRP) is an RNA-binding protein that promotes mRNA decay and thereby negatively regulates cytokine expression at the post-transcriptional level. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by dysregulated cytokine expression causing multiple organ manifestations; MRL-Faslpr mice are an established mouse model to study lupus disease pathogenesis. To investigate the impact of KSRP on lupus disease progression, we generated KSRP-deficient MRL-Faslpr mice (MRL-Faslpr/KSRP−/− mice). In line with the predicted role of KSRP as a negative regulator of cytokine expression, lupus nephritis was augmented in MRL-Faslpr/KSRP−/− mice. Increased infiltration of immune cells, especially of IFN-γ producing T cells and macrophages, driven by enhanced expression of T cell-attracting chemokines and adhesion molecules, seems to be responsible for worsened kidney morphology. Reduced expression of the anti-inflammatory interleukin-1 receptor antagonist may be another reason for severe inflammation. The increase of FoxP3+ T cells detected in the kidney seems unable to dampen the massive kidney inflammation. Interestingly, lymphadenopathy was reduced in MRL-Faslpr/KSRP−/− mice. Altogether, KSRP appears to have a complex role in immune regulation; however, it is clearly able to ameliorate lupus nephritis.

Regenereation in periodontics

2018 ◽  
Author(s):  
Murtaza Kaderi ◽  
Mohsin Ali ◽  
Alfiya Ali ◽  
Tasneem Kaderi
Keyword(s):  
Tissue Engineering ◽  
Clinical Practice ◽  
Periodontal Disease ◽  
Disease Progression ◽  
Tissue Regeneration ◽  
Surgical Procedures ◽  
Periodontal Regeneration ◽  
Guided Tissue Regeneration ◽  
Periodontal Tissues ◽  
Extensive Documentation

The goals of periodontal therapy are to arrest of periodontal disease progression and to attain the regeneration of the periodontal apparatus. Osseous grafting and Guided tissue regeneration (GTR) are the two techniques with the most extensive documentation of periodontal regeneration. However, these techniques offer limited potential towards regenerating the periodontal tissues. Recent surgical procedures and application of newer materials aim at greater and more predictable regeneration with the concept of tissue engineering for enhanced periodontal regeneration and functional attachment have been developed, analyzed, and employed in clinical practice

scholarly journals AT1 and AT2 Receptor Knockout Changed Osteonectin and Bone Density in Mice in Periodontal Inflammation Experimental Model

2021 ◽  
Vol 22 (10) ◽  
pp. 5217
Author(s):  
Maria Laura de Souza Lima ◽  
Caroline Addison Carvalho Xavier de Medeiros ◽  
Gerlane Coelho Bernardo Guerra ◽  
Robson Santos ◽  
Michael Bader ◽  
...  
Keyword(s):  
Bone Density ◽  
Bone Loss ◽  
Experimental Model ◽  
At2 Receptor ◽  
Micro Ct ◽  
Rt Pcr ◽  
Osteoblast Cells ◽  
Periodontal Inflammation ◽  
Bone Trabeculae

Background: The aim of this study was to evaluate the role of AT1 and AT2 receptors in a periodontal inflammation experimental model. Methods: Periodontal inflammation was induced by LPS/Porphyromonas gingivalis. Maxillae, femur, and vertebra were scanned using Micro-CT. Maxillae were analyzed histopathologically, immunohistochemically, and by RT-PCR. Results: The vertebra showed decreased BMD in AT1 H compared with WT H (p < 0.05). The femur showed increased Tb.Sp for AT1 H and AT2 H, p < 0.01 and p < 0.05, respectively. The Tb.N was decreased in the vertebra (WT H-AT1 H: p < 0.05; WT H-AT2 H: p < 0.05) and in the femur (WT H-AT1 H: p < 0.01; WT H-AT2 H: p < 0.05). AT1 PD increased linear bone loss (p < 0.05) and decreased osteoblast cells (p < 0.05). RANKL immunostaining was intense for AT1 PD and WT PD (p < 0.001). OPG was intense in the WT H, WT PD, and AT2 PD when compared to AT1 PD (p < 0.001). AT1 PD showed weak immunostaining for osteocalcin compared with WT H, WT PD, and AT2 PD (p < 0.001). AT1 H showed significantly stronger immunostaining for osteonectin in fibroblasts compared to AT2 H (p < 0.01). Conclusion: AT1 receptor knockout changed bone density, the quality and number of bone trabeculae, decreased the number of osteoblast cells, and increased osteonectin in fibroblasts.

scholarly journals cFLIP-L Inhibits p38 MAPK Activation

2003 ◽  
Vol 278 (29) ◽  
pp. 26831-26837 ◽  
Author(s):  
Annette Grambihler ◽  
Hajime Higuchi ◽  
Steven F. Bronk ◽  
Gregory J. Gores
Keyword(s):  
P38 Mapk ◽  
Mapk Activation

scholarly journals The Protective Effect of Rhizoma Dioscoreae Extract against Alveolar Bone Loss in Ovariectomized Rats via Regulating Wnt and p38 MAPK Signaling

Nutrients ◽  
2014 ◽  
Vol 6 (12) ◽  
pp. 5853-5870 ◽  
Author(s):  
Zhiguo Zhang ◽  
Lihua Xiang ◽  
Dong Bai ◽  
Wenlai Wang ◽  
Yan Li ◽  
...  
Keyword(s):  
Bone Loss ◽  
Protective Effect ◽  
P38 Mapk ◽  
Alveolar Bone ◽  
Mapk Signaling ◽  
Alveolar Bone Loss ◽  
Ovariectomized Rats
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