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https://www.readbyqxmd.com/read/29047262/current-understanding-of-rank-signaling-in-osteoclast-differentiation-and-maturation
#1
Jin Hee Park, Na Kyung Lee, Soo Young Lee
Osteoclasts are bone-resorbing cells that are derived from hematopoietic precursor cells and require macrophage-colony stimulating factor and receptor activator of nuclear factor-κB ligand (RANKL) for their survival, proliferation, differentiation, and activation. The binding of RANKL to its receptor RANK triggers osteoclast precursors to differentiate into osteoclasts. This process depends on RANKL-RANK signaling, which is temporally regulated by various adaptor proteins and kinases. Here we summarize the current understanding of the mechanisms that regulate RANK signaling during osteoclastogenesis...
October 17, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28955231/nardosinone-suppresses-rankl-induced-osteoclastogenesis-and-attenuates-lipopolysaccharide-induced-alveolar-bone-resorption
#2
Chenguang Niu, Fei Xiao, Keyong Yuan, XuChen Hu, Wenzhen Lin, Rui Ma, Xiaoling Zhang, Zhengwei Huang
Periodontitis is a chronic inflammatory disease that damages the integrity of the tooth-supporting tissues, known as the periodontium, and comprising the gingiva, periodontal ligament and alveolar bone. In this study, the effects of nardosinone (Nd) on bone were tested in a model of lipopolysaccharide (LPS)-induced alveolar bone loss, and the associated mechanisms were elucidated. Nd effectively suppressed LPS-induced alveolar bone loss and reduced osteoclast (OC) numbers in vivo. Nd suppressed receptor activator of nuclear factor-κB ligand (RANKL)-mediated OC differentiation, bone resorption, and F-actin ring formation in a dose-dependent manner...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28910360/transgelin-2-is-upregulated-on-activated-b-cells-and-expressed-in-hyperplastic-follicles-in-lupus-erythematosus-patients
#3
Kaori Kiso, Hajime Yoshifuji, Takuma Oku, Masaki Hikida, Koji Kitagori, Yoshitaka Hirayama, Toshiki Nakajima, Hironori Haga, Tatsuaki Tsuruyama, Aya Miyagawa-Hayashino
Transgelin-2 (TAGLN2) is an actin-binding protein that controls actin stability and promotes T cell activation. TAGLN2 is also expressed on B-cells but its function in B-cells is unknown. We found that TAGLN2-expressing B-cells were localized in the germinal center (GC) of secondary lymphoid tissues and TAGLN2 mRNA was significantly upregulated after IgM+IgG stimulation in primary human B-cells, suggesting that TAGLN2 was upregulated upon B-cell activation. In support of this, lymph nodes (LNs) from patients with systemic lupus erythematosus (SLE), in which the intense GC activity have been recognized, showed increased TAGLN2 expression in B-cells compared to control LNs...
2017: PloS One
https://www.readbyqxmd.com/read/28878675/inhibition-of-collagen-induced-platelet-aggregation-by-the-secobutanolide-secolincomolide-a-from-lindera-obtusiloba-blume
#4
Sang-Hyuk Jung, Joo-Hui Han, Hyun-Soo Park, Jung-Jin Lee, Seo Young Yang, Young Ho Kim, Kyung-Sun Heo, Chang-Seon Myung
Atherothrombosis is one of the main underlying cause of cardiovascular diseases. In addition to treating atherothrombosis with antithrombotic agents, there is growing interest in the role of natural food products and biologically active ingredients for the prevention and treatment of cardiovascular diseases. This study aimed to investigate the effect of secolincomolide A (3) isolated from Lindera obtusiloba Blume on platelet activity and identify possible signaling pathways. In our study, the antiplatelet activities of 3 were measured by collagen-induced platelet aggregation and serotonin secretion in freshly isolated rabbit platelets...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28842683/a-novel-ruthenium-ii-derived-organometallic-compound-tq-6-potently-inhibits-platelet-aggregation-ex-vivo-and-in-vivo-studies
#5
Chih-Hsuan Hsia, Marappan Velusamy, Joen-Rong Sheu, Themmila Khamrang, Thanasekaran Jayakumar, Wan-Jung Lu, Kuan-Hung Lin, Chao-Chien Chang
Arterial thrombosis plays a key role in cardiovascular diseases. Hence, developing more effective antithrombotic agents is necessary. We designed a ruthenium (II)-derived complex, [Ru(η(6)-cymene)2-(1H-benzoimidazol-2-yl)-quinoline Cl]BF4 (TQ-6), as a new antiplatelet drug. TQ-6 (0.3 µM) exhibited extremely strong inhibitory activity against platelet aggregation, Src, and Syk phosphorylation stimulated by agonists in human platelets. In collagen-activated platelets, TQ-6 also inhibited ATP-release, [Ca(+2)]i, P-selectin expression, FITC-PAC-1 binding, and hydroxyl radical formation, as well as the phosphorylation of phospholipase Cγ2, protein kinase C, mitogen-activated protein kinases, and Akt...
August 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28836860/enhancement-or-inhibition-of-plc%C3%AE-2-expression-in-rat-hepatocytes-by-recombinant-adenoviral-vectors-that-contain-full-length-gene-or-sirna
#6
X G Chen, Y M Liu, Q X Lv, J Ma
We investigated the effects of recombinant adenovirus vectors that overexpress or silence PLCγ2 on the expression of this gene during hepatocyte proliferation. Hepatocytes were isolated, identified by immunofluorescent cytochemical staining and infected by previously constructed Ad-PLCγ2 and Ad-PLCγ2 siRNA1, siRNA2 and siRNA3. Green fluorescent protein (GFP) expression was observed by fluorescence microscopy. Infection percentage was calculated by flow cytometry. mRNA and protein levels of PLCγ2 were detected by quantitative reverse transcription-PCR (qRT-PCR) and western blotting, respectively...
August 24, 2017: Biotechnic & Histochemistry: Official Publication of the Biological Stain Commission
https://www.readbyqxmd.com/read/28775078/tlr2-plays-a-key-role-in-platelet-hyperreactivity-and-accelerated-thrombosis-associated-with-hyperlipidemia
#7
Sudipta Biswas, Alejandro Zimman, Detao Gao, Tatiana V Byzova, Eugene A Podrez
RATIONALE: Platelet hyperreactivity, which is common in many pathological conditions, is associated with increased atherothrombotic risk. The mechanisms leading to platelet hyperreactivity are complex and not yet fully understood. OBJECTIVE: Platelet hyperreactivity and accelerated thrombosis, specifically in dyslipidemia, have been mechanistically linked to the accumulation in the circulation of a specific group of oxidized phospholipids (oxPCCD36) that are ligands for the platelet pattern recognition receptor CD36...
September 29, 2017: Circulation Research
https://www.readbyqxmd.com/read/28711718/phospholipase-d1-is-a-regulator-of-platelet-mediated-inflammation
#8
Meike Klier, Nina Sarah Gowert, Sven Jäckel, Christoph Reinhardt, Margitta Elvers
Glycoprotein (GP)Ib is not only required for stable thrombus formation but for platelet-mediated inflammatory responses. Phospholipase (PL)D1 is essential for GPIb-dependent aggregate formation under high shear conditions while nothing is known about PLD1-induced regulation of GPIb in platelet-mediated inflammation and the underlying mechanisms. This study aimed to investigate the relevance of PLD1 for platelet-mediated endothelial and leukocyte recruitment and activation in vitro and in vivo. Pld1(-/-) platelets showed strongly reduced adhesion to TNFα stimulated endothelial cells (ECs) under high shear conditions ex vivo...
July 12, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28705934/gq-pathway-regulates-proximal-c-type-lectin-like-receptor-2-clec-2-signaling-in-platelets
#9
COMPARATIVE STUDY
Rachit Badolia, Vaishali Inamdar, Bhanu Kanth Manne, Carol Dangelmaier, Johannes A Eble, Satya P Kunapuli
Platelets play a key role in the physiological hemostasis or pathological process of thrombosis. Rhodocytin, an agonist of the C-type lectin-like receptor-2 (CLEC-2), elicits powerful platelet activation signals in conjunction with Src family kinases (SFKs), spleen tyrosine kinase (Syk), and phospholipase γ2 (PLCγ2). Previous reports have shown that rhodocytin-induced platelet aggregation depends on secondary mediators such as thromboxane A2 (TxA2) and ADP, which are agonists for G-protein-coupled receptors (GPCRs) on platelets...
September 1, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28704925/licochalcone-a-prevents-platelet-activation-and-thrombus-formation-through-the-inhibition-of-plc%C3%AE-2-pkc-akt-and-mapk-pathways
#10
Li-Ming Lien, Kuan-Hung Lin, Li-Ting Huang, Mei-Fang Tseng, Hou-Chang Chiu, Ray-Jade Chen, Wan-Jung Lu
Platelet activation is involved in cardiovascular diseases, such as atherosclerosis and ischemic stroke. Licochalcone A (LA), an active ingredient of licorice, exhibits multiple biological activities such as anti-oxidation and anti-inflammation. However, its role in platelet activation remains unclear. Therefore, the study investigated the antiplatelet mechanism of LA. Our data revealed that LA (2-10 μM) concentration dependently inhibited platelet aggregation induced by collagen, but not thrombin and U46619...
July 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28368423/myc-enhances-b-cell-receptor-signaling-in-precancerous-b-cells-and-confers-resistance-to-btk-inhibition
#11
T K Moyo, C S Wilson, D J Moore, C M Eischen
Dysregulation of the oncogenic transcription factor MYC induces B-cell transformation and is a driver for B-cell non-Hodgkin lymphoma (B-NHL). MYC overexpression in B-NHL is associated with more aggressive phenotypes and poor prognosis. Although genomic studies suggest a link between MYC overexpression and B-cell receptor (BCR) signaling molecules in B-NHL, signaling pathways essential to Myc-mediated B-cell transformation have not been fully elucidated. We utilized intracellular phospho-flow cytometry to investigate the relationship between Myc and BCR signaling in pre-malignant B cells...
August 10, 2017: Oncogene
https://www.readbyqxmd.com/read/28272351/methyl-gallate-inhibits-osteoclast-formation-and-function-by-suppressing-akt-and-btk-plc%C3%AE-2-ca-2-signaling-and-prevents-lipopolysaccharide-induced-bone-loss
#12
Jong Min Baek, Ju-Young Kim, Chang Hoon Lee, Kwon-Ha Yoon, Myeung Su Lee
In the field of bone research, various natural derivatives have emerged as candidates for osteoporosis treatment by targeting abnormally elevated osteoclastic activity. Methyl gallate, a plant-derived phenolic compound, is known to have numerous pharmacological effects against inflammation, oxidation, and cancer. Our purpose was to explore the relation between methyl gallate and bone metabolism. Herein, we performed screening using methyl gallate by tartrate resistant acid phosphatase (TRAP) staining and revealed intracellular mechanisms responsible for methyl gallate-mediated regulation of osteoclastogenesis by Western blotting and quantitative reverse transcription polymerase chain reaction (RT-PCR)...
March 7, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28235842/acquired-mutations-associated-with-ibrutinib-resistance-in-waldenstr%C3%A3-m-macroglobulinemia
#13
Lian Xu, Nicholas Tsakmaklis, Guang Yang, Jiaji G Chen, Xia Liu, Maria Demos, Amanda Kofides, Christopher J Patterson, Kirsten Meid, Joshua Gustine, Toni Dubeau, M Lia Palomba, Ranjana Advani, Jorge J Castillo, Richard R Furman, Zachary R Hunter, Steven P Treon
Ibrutinib produces high response rates and durable remissions in Waldenström macroglobulinemia (WM) that are impacted by MYD88 and CXCR4(WHIM) mutations. Disease progression can develop on ibrutinib, although the molecular basis remains to be clarified. We sequenced sorted CD19(+) lymphoplasmacytic cells from 6 WM patients who progressed after achieving major responses on ibrutinib using Sanger, TA cloning and sequencing, and highly sensitive and allele-specific polymerase chain reaction (AS-PCR) assays that we developed for Bruton tyrosine kinase (BTK) mutations...
May 4, 2017: Blood
https://www.readbyqxmd.com/read/28212557/using-high-sensitivity-sequencing-for-the-detection-of-mutations-in-btk-and-plc%C3%AE-2-genes-in-cellular-and-cell-free-dna-and-correlation-with-progression-in-patients-treated-with-btk-inhibitors
#14
Adam Albitar, Wanlong Ma, Ivan DeDios, Jeffrey Estella, Inhye Ahn, Mohammed Farooqui, Adrian Wiestner, Maher Albitar
Patients with chronic lymphocytic leukemia (CLL) that develop resistance to Bruton tyrosine kinase (BTK) inhibitors are typically positive for mutations in BTK or phospholipase c gamma 2 (PLCγ2). We developed a high sensitivity (HS) assay utilizing wild-type blocking polymerase chain reaction achieved via bridged and locked nucleic acids. We used this high sensitivity assay in combination with Sanger sequencing and next generation sequencing (NGS) and tested cellular DNA and cell-free DNA (cfDNA) from patients with CLL treated with the BTK inhibitor, ibrutinib...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28054640/honokiol-as-a-specific-collagen-receptor-glycoprotein-vi-antagonist-on-human-platelets-functional-ex-vivo-and-in-vivo-studies
#15
Tzu-Yin Lee, Chao-Chien Chang, Wan-Jung Lu, Ting-Lin Yen, Kuan-Hung Lin, Pitchairaj Geraldine, Jiun-Yi Li, Joen-Rong Sheu
Honokiol, derived from Magnolia officinalis, has various pharmacological properties. Platelet activation plays a critical role in cardiovascular diseases. Honokiol has been reported to inhibit collagen-stimulated rabbit platelet aggregation. However, detailed further studies on the characteristics and functional activity of honokiol in platelet activation are relatively lacking. In the present study, honokiol specifically inhibited platelet aggregation and Ca(+2) ion mobilization stimulated with collagen or convulxin, an agonist of glycoprotein (GP) VI, but not with aggretin, an agonist of integrin α2β1...
January 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/27941021/phospholipase-c%C3%AE-1-plc%C3%AE-1-controls-osteoclast-numbers-via-colony-stimulating-factor-1-csf-1-dependent-diacylglycerol-%C3%AE-catenin-cyclind1-pathway
#16
Zhengfeng Yang, Seokho Kim, Sahil Mahajan, Ali Zamani, Roberta Faccio
Phospholipases Cγ (PLCγ) 1 and 2 are a class of highly homologous enzymes modulating a variety of cellular pathways through production of inositol 1,4,5-trisphosphate and diacylglycerol (DAG). Our previous studies demonstrated the importance of PLCγ2 in osteoclast (OC) differentiation by modulating inositol 1,4,5-trisphosphate-mediated calcium oscillations and the up-regulation of the transcription factor NFATc1. Surprisingly, despite being expressed throughout osteoclastogenesis, PLCγ1 did not compensate for PLCγ2 deficiency...
January 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27912872/anti-allergic-potential-of-typhonium-blumei-inhibition-of-degranulation-via-suppression-of-pi3k-plc%C3%AE-2-phosphorylation-and-calcium-influx
#17
Michal Korinek, Kuan-Ming Chen, Yu-Han Jiang, Mohamed El-Shazly, Joel Stocker, Chon-Kit Chou, Tsong-Long Hwang, Yang-Chang Wu, Bing-Hung Chen, Fang-Rong Chang
BACKGROUND: Typhonium blumei Nicolson & Sivadasan (Araceae) is a traditional Chinese medicinal herb possessing detumescent, detoxifying, and anti-inflammatory activities. It is used in Taiwan as a folk medicine to treat cancer and inflammatory diseases. Typhonium blumei is usually not distinguished from Typhonium roxburghii Schott and they are commonly used interchangeably. PURPOSE: To evaluate and compare the anti-allergic and anti-inflammatory properties of T...
December 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/27903679/the-bruton-tyrosine-kinase-btk-inhibitor-acalabrutinib-demonstrates-potent-on-target-effects-and-efficacy-in-two-mouse-models-of-chronic-lymphocytic-leukemia
#18
Sarah E M Herman, Arnau Montraveta, Carsten U Niemann, Helena Mora-Jensen, Michael Gulrajani, Fanny Krantz, Rose Mantel, Lisa L Smith, Fabienne McClanahan, Bonnie K Harrington, Dolors Colomer, Todd Covey, John C Byrd, Raquel Izumi, Allard Kaptein, Roger Ulrich, Amy J Johnson, Brian J Lannutti, Adrian Wiestner, Jennifer A Woyach
Purpose: Acalabrutinib (ACP-196) is a novel, potent, and highly selective Bruton tyrosine kinase (BTK) inhibitor, which binds covalently to Cys481 in the ATP-binding pocket of BTK. We sought to evaluate the antitumor effects of acalabrutinib treatment in two established mouse models of chronic lymphocytic leukemia (CLL).Experimental Design: Two distinct mouse models were used, the TCL1 adoptive transfer model where leukemic cells from Eμ-TCL1 transgenic mice are transplanted into C57BL/6 mice, and the human NSG primary CLL xenograft model...
June 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27896950/ppar%C3%AE-agonists-negatively-regulate-%C3%AE-iib%C3%AE-3-integrin-outside-in-signaling-and-platelet-function-through-up-regulation-of-protein-kinase-a-activity
#19
A J Unsworth, N Kriek, A P Bye, K Naran, T Sage, G D Flora, J M Gibbins
Essentials peroxisome proliferator-activated receptor γ (PPARγ) agonists inhibit platelet function. PPARγ agonists negatively regulate outside-in signaling via integrin αIIbβ3. PPARγ agonists disrupt the interaction of Gα13 with integrin β3. This is attributed to an upregulation of protein kinase A activity. SUMMARY: Background Agonists for the peroxisome proliferator-activated receptor (PPARγ) have been shown to have inhibitory effects on platelet activity following stimulation by GPVI and GPCR agonists...
February 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/27883180/mitochondrial-reactive-oxygen-species-suppress-humoral-immune-response-through-reduction-of-cd19-expression-in-b-cells-in-mice
#20
Masato Ogura, Takeshi Inoue, Junko Yamaki, Miwako K Homma, Tomohiro Kurosaki, Yoshimi Homma
Reactive oxygen species (ROS) are implicated in the modulation of diverse processes including immune responses. To evaluate the effects of metabolic ROS produced by mitochondria on B-cell function and development, we created transgenic (Tg) mice expressing a phosphorylation-defective mutant of succinate dehydrogenase A in B cells (bSDHA(Y215F) ). Splenic B cells in male, but not female, bSDHA(Y215F) mice produced three times more ROS than those in the control mice, and had decreased production of IgM, IgG1 , and IgG3 , and affinity maturation of IgG1 against T-cell-dependent antigens...
February 2017: European Journal of Immunology
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