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https://www.readbyqxmd.com/read/28079882/stability-of-the-cancer-target-ddias-is-regulated-by-the-chip-hsp70-pathway-in-lung-cancer-cells
#1
Kyoung-Jae Won, Joo-Young Im, Bo-Kyung Kim, Hyun Seung Ban, Young-Jin Jung, Kyeong Eun Jung, Misun Won
DNA damage-induced apoptosis suppressor (DDIAS) rescues lung cancer cells from apoptosis in response to DNA damage. DDIAS is transcriptionally activated by NFATc1 and EGF-mediated ERK5/MEF2B, leading to cisplatin resistance and cell invasion. Therefore, DDIAS is suggested as a therapeutic target for lung cancer. Here, we report that DDIAS stability is regulated by E3 U-box ubiquitin ligase carboxyl terminus of HSP70-interacting protein (CHIP)-mediated proteasomal degradation. We first isolated CHIP as an interacting partner of DDIAS by yeast two-hybrid screening...
January 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28067799/excavatolide-b-attenuates-rheumatoid-arthritis-through-the-inhibition-of-osteoclastogenesis
#2
Yen-You Lin, Yen-Hsuan Jean, Hsin-Pai Lee, Sung-Chun Lin, Chieh-Yu Pan, Wu-Fu Chen, Shu-Fen Wu, Jui-Hsin Su, Kuan-Hao Tsui, Jyh-Horng Sheu, Ping-Jyun Sung, Zhi-Hong Wen
Osteoclasts are multinucleated giant cells of macrophage/monocyte lineage, and cell differentiation with the upregulation of osteoclast-related proteins is believed to play a major role in the destruction of the joints in the course of rheumatoid arthritis (RA). Pro-inflammatory cytokines, such as interleukin-17A (IL-17A) and macrophage colony-stimulating factor (M-CSF), can be overexpressed in RA and lead to osteoclastogenesis. In a previous study, we found that cultured-type soft coral-derived excavatolide B (Exc-B) exhibited anti-inflammatory properties...
January 6, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28056236/-cd137-cd137l-signaling-promotes-angiogenesis-in-atherosclerosis-plaque-of-mice-through-activating-nuclear-factor-of-activated-t-cells-c1
#3
J Y Weng, J C Yan, Y Chen, Z Q Wang, C P Wang, C Shao
Objective: To explore whether CD137-CD137L signaling can promote angiogenesis in atherosclerosis plaque via activating nuclear factor of activated T cells c1 (NFATc1). Methods: Apolipoprotein E knock out mice were divided into the following groups: control group (n=5), CD137 activated group(n=5)and CD137 inhibited group (n=5). Immunohistochemistry was performed to detect the expression of CD31 in aortic plaque. Endothelial cells (bEnd.3) were purchased from ATCC and divided into the following groups: control group, IgG isotype control group, CD137 activated group and CD137 inhibited group...
December 24, 2016: Zhonghua Xin Xue Guan Bing za Zhi
https://www.readbyqxmd.com/read/28050266/from-slow-to-fast-hypogravity-induced-remodeling-of-muscle-fiber-myosin-phenotype
#4
B S Shenkman
Skeletal muscle consists of different fiber types arranged in a mosaic pattern. These fiber types are characterized by specific functional properties. Slow-type fibers demonstrate a high level of fatigue resistance and prolonged contraction duration, but decreased maximum contraction force and velocity. Fast-type fibers demonstrate high contraction force and velocity, but profound fatigability. During the last decades, it has been discovered that all these properties are determined by the predominance of slow or fast myosin-heavy-chain (MyHC) isoforms...
October 2016: Acta Naturae
https://www.readbyqxmd.com/read/27974827/investigating-the-human-calcineurin-interaction-network-using-the-%C3%AF-%C3%A9-lxvp-slim
#5
Sarah R Sheftic, Rebecca Page, Wolfgang Peti
Ser/thr phosphorylation is the primary reversible covalent modification of proteins in eukaryotes. As a consequence, it is the reciprocal actions of kinases and phosphatases that act as key molecular switches to fine tune cellular events. It has been well documented that ~400 human ser/thr kinases engage substrates via consensus phosphosite sequences. Strikingly, we know comparatively little about the mechanism by which ~40 human protein ser/thr phosphatases (PSPs) dephosphorylate ~15000 different substrates with high specificity...
December 15, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27965942/attenuation-of-rankl-induced-osteoclast-formation-via-p38-mediated-nfatc1-signaling-pathways-by-extract-of-euphorbia-lathyris-l
#6
Ju-Hee Kang, Hyojung Lim, Ji-Eun Jeong, Mijung Yim
BACKGROUND: Osteoclasts are the only cell type capable of breaking down bone matrix, and its excessive activation is responsible for the development of bone-destructive diseases. Euphorbia lathyris L. (ELL) is an herbal plant that belongs to the Euphorbiaceae family. This study investigated the effects of the methanol extract of the aerial part of ELL on receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclast formation and signaling pathways. METHODS: Osteoclasts were formed by co-culturing mouse bone marrow with osteoblasts or by culturing mouse bone marrow-derived macrophages (BMMs) with macrophage colony-stimulating factor (M-CSF) and RANKL...
November 2016: Journal of Bone Metabolism
https://www.readbyqxmd.com/read/27941021/plc%C3%AE-1-controls-osteoclast-numbers-via-csf-1-dependent-diacylglycerol-%C3%AE-catenin-cyclind1-pathway
#7
Zhengfeng Yang, Seokho Kim, Sahil Mahajan, Ali Zamani, Roberta Faccio
Phospholipase C gamma (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 (IP3) and diacylglycerol (DAG). Our previous studies demonstrated the importance of PLCγ2 in osteoclast (OC) differentiation by modulating IP3-mediated calcium oscillations and the upregulation of the transcription factor NFATc1. Surprisingly, despite being expressed throughout osteoclastogenesis, PLCγ1 did not compensate for PLCγ2 deficiency...
December 9, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27940164/rankl-release-from-self-assembling-nanofiber-hydrogels-for-inducing-osteoclastogenesis-in-vitro
#8
James Z Xing, Lei Lu, Larry D Unsworth, Paul W Major, Michael R Doschak, Neelambar R Kaipatur
PURPOSE: To develop a nanofiber hydrogel (NF-hydrogel) for sustained and controlled release of the recombinant receptor activator of NF-kB ligand; (RANKL) and to characterize the release kinetics and bioactivity of the released RANKL. METHODS: Various concentrations of fluorescently-labelled RANKL protein were added to NF-hydrogels, composed of Acetyl-(Arg-Ala-Asp-Ala)4-CONH2 [(RADA)4] of different concentrations, to investigate the resulting in vitro release rates...
December 7, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/27935966/the-transcription-factor-nfatc2-regulates-%C3%AE-cell-proliferation-and-genes-associated-with-type-2-diabetes-in-mouse-and-human-islets
#9
Mark P Keller, Pradyut K Paul, Mary E Rabaglia, Donnie S Stapleton, Kathryn L Schueler, Aimee Teo Broman, Shuyun Isabella Ye, Ning Leng, Christopher J Brandon, Elias Chaibub Neto, Christopher L Plaisier, Shane P Simonett, Melkam A Kebede, Gloria M Sheynkman, Mark A Klein, Nitin S Baliga, Lloyd M Smith, Karl W Broman, Brian S Yandell, Christina Kendziorski, Alan D Attie
Human genome-wide association studies (GWAS) have shown that genetic variation at >130 gene loci is associated with type 2 diabetes (T2D). We asked if the expression of the candidate T2D-associated genes within these loci is regulated by a common locus in pancreatic islets. Using an obese F2 mouse intercross segregating for T2D, we show that the expression of ~40% of the T2D-associated genes is linked to a broad region on mouse chromosome (Chr) 2. As all but 9 of these genes are not physically located on Chr 2, linkage to Chr 2 suggests a genomic factor(s) located on Chr 2 regulates their expression in trans...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27920208/genetic-modification-of-er-hoxb8-osteoclast-precursors-using-crispr-cas9-as-a-novel-way-to-allow-studies-on-osteoclast-biology
#10
Irene Di Ceglie, Guus G H van den Akker, Giuliana Ascone, Bas Ten Harkel, Hans Häcker, Fons A J van de Loo, Marije I Koenders, Peter M van der Kraan, Teun J de Vries, Thomas Vogl, Johannes Roth, Peter L E M van Lent
Osteoclasts are cells specialized in bone resorption. Currently, studies on murine osteoclasts are primarily performed on bone marrow-derived cells with the use of many animals and limited cells available. ER-Hoxb8 cells are conditionally immortalized monocyte/macrophage murine progenitor cells, recently described to be able to differentiate toward functional osteoclasts. Here, we produced an ER-Hoxb8 clonal cell line from C57BL/6 bone marrow cells that strongly resembles phenotype and function of the conventional bone marrow-derived osteoclasts...
December 5, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27917924/rcans-regulate-the-convergent-roles-of-nfatc1-in-bone-homeostasis
#11
Jung Ha Kim, Kabsun Kim, Inyoung Kim, Semun Seong, Byung-Chul Jeong, Kwang-Il Nam, Kyung Keun Kim, Jeffery D Molkentin, Nacksung Kim
Activation of calcineurin-dependent nuclear factor of activated T cells c1 (NFATc1) is convergent for normal bone homeostasis. NFATc1 regulates both osteoclastogenesis and osteoblastogenesis. Here we investigated the roles of regulator of calcineurin (RCAN) genes in bone homeostasis. RCANs function as potent physiological inhibitors of calcineurin. Overexpression of RCANs in osteoclast precursor cells attenuated osteoclast differentiation, while their overexpression in osteoblasts enhanced osteoblast differentiation and function...
December 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27913299/the-inhibitory-effect-of-beta-lapachone-on-rankl-induced-osteoclastogenesis
#12
Dong Ryun Gu, Joon No Lee, Gi-Su Oh, Hyung Jin Kim, Min Seuk Kim, Seoung Hoon Lee
β-lapachone (β-L) is a substrate of reduced nicotinamide adenine dinucleotide (NADH): quinone oxidoreductase 1 (NQO1). NQO1 reduces quinones to hydroquinones using NADH as an electron donor and consequently increases the intracellular NAD+/NADH ratio. The activation of NQO1 by β-L has beneficial effects on several metabolic syndromes, such as obesity, hypertension, and renal injury. However, the effect of β-L on bone metabolism remains unclear. Here, we show that β-L might be a potent inhibitor of receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27897222/nadph-oxidase-gp91-phox-contributes-to-rankl-induced-osteoclast-differentiation-by-upregulating-nfatc1
#13
In Soon Kang, Chaekyun Kim
Bone-marrow derived monocyte-macrophages (BMMs) differentiate into osteoclasts by M-CSF along subsequent RANKL stimulation possibly in collaboration with many other unknown cytokines released by pre- or mature osteoblasts. The differentiation process requires receptor activator of nuclear factor kappa-B ligand (RANKL)/RANK signaling and reactive oxygen species (ROS) such as superoxide anion (O2(•-)). Gp91(phox), a plasma membrane subunit of NADPH oxidase (Nox), is constitutively expressed in BMMs and plays a major role in superoxide anion production...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27896363/oxygen-ultra-fine-bubbles-water-administration-prevents-bone-loss-of-glucocorticoid-induced-osteoporosis-in-mice-by-suppressing-osteoclast-differentiation
#14
T Noguchi, K Ebina, M Hirao, T Morimoto, K Koizumi, K Kitaguchi, H Matsuoka, T Iwahashi, H Yoshikawa
: Oxygen ultra-fine bubbles (OUB) saline injection prevents bone loss of glucocorti\coid-induced osteoporosis in mice, and OUB inhibit osteoclastogenesis via RANK-TRAF6-c-Fos-NFATc1 signaling and RANK-p38 MAPK signaling in vitro. INTRODUCTION: Ultra-fine bubbles (<200 nm in diameter) have several unique properties, and they are tested in various medical fields. The purpose of this study was to investigate the effects of oxygen ultra-fine bubbles (OUB) on glucocorticoid-induced osteoporosis (GIO) model mice...
November 28, 2016: Osteoporosis International
https://www.readbyqxmd.com/read/27895178/conserved-region-c-functions-to-regulate-pd-1-expression-and-subsequent-cd8-t-cell-memory
#15
Alexander P R Bally, Yan Tang, Joshua T Lee, Benjamin G Barwick, Ryan Martinez, Brian D Evavold, Jeremy M Boss
Expression of programmed death 1 (PD-1) on CD8 T cells promotes T cell exhaustion during chronic Ag exposure. During acute infections, PD-1 is transiently expressed and has the potential to modulate CD8 T cell memory formation. Conserved region C (CR-C), a promoter proximal cis-regulatory element that is critical to PD-1 expression in vitro, responds to NFATc1, FoxO1, and/or NF-κB signaling pathways. Here, a CR-C knockout mouse was established to determine its role on PD-1 expression and the corresponding effects on T cell function in vivo...
January 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27879421/loss-of-notch3-signaling-enhances-osteogenesis-of-mesenchymal-stem-cells-from-mandibular-torus
#16
X W Dou, W Park, S Lee, Q Z Zhang, L R Carrasco, A D Le
Mandibular torus (MT) is a common intraoral osseous outgrowth located on the lingual surface of the mandible. Histologic features include hyperplastic bone consisting of mature cortical and trabecular bone. Some theories on the etiology of MT have been postulated, such as genetic factors, masticatory hyperfunction, trauma, and continued growth, but the underlying mechanism remains largely unknown. In this study, we investigated the potential role of mesenchymal stem cells (MSCs) derived from human MT in the pathogenesis of bone outgrowth...
November 22, 2016: Journal of Dental Research
https://www.readbyqxmd.com/read/27871781/crocin-inhibits-rankl-induced-osteoclast-formation-and-bone-resorption-by-suppressing-nf-%C3%AE%C2%BAb-signaling-pathway-activation
#17
Lijia Fu, Fang Pan, Yong Jiao
Crocin is a dietary compound with antioxidant and anti-inflammatory properties, but its effects on bone resorption have not been well characterized. Here we address this issue by examining the direct effects of crocin on osteoclast cells in vitro. Osteoclastogenesis was induced by RANKL (receptor activator of NF-κB ligand) in mouse bone marrow-derived macrophages in the absence or presence of crocin at various concentrations. Further, the bone resorption activity of mature osteoclast treated with crocin was assessed by pit assay...
November 15, 2016: Immunobiology
https://www.readbyqxmd.com/read/27858552/fluvastatin-inhibits-osteoclast-differentiation-and-p-gingivalis-lipopolysaccharide-induced-alveolar-bone-erosion-in-mice
#18
Nitin Kumar Pokhrel, Yong-Gun Kim, Jae-Young Kim, Hong-Hee Kim, Youngkyun Lee
BACKGROUND: Statins have been widely used to treat hypercholesterolemia. In addition to the inhibition of cholesterol synthesis, recent reports suggest bone anabolic property of statins. However, little notice has been paid to the direct effect of statins on osteoclastogenesis and bone resorption. METHODS: The effect of fluvastatin on osteoclast differentiation was determined using in vitro culture of mouse bone marrow macrophages (BMMs) in the presence of macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa B ligand (RANKL)...
November 18, 2016: Journal of Periodontology
https://www.readbyqxmd.com/read/27856256/pulsed-electromagnetic-field-inhibits-rankl-dependent-osteoclastic-differentiation-in-raw264-7-cells-through-the-ca-2-calcineurin-nfatc1-signaling-pathway
#19
Jie Zhang, Haixia Xu, Zhongyu Han, Ping Chen, Qiang Yu, Yutian Lei, Zongze Li, Ming Zhao, Jing Tian
Pulsed electromagnetic field (PEMF) has been reported to improve bone healing in osteoporosis patients. However, the precise mechanism has remained largely unknown. This study aimed to investigate the effects of PEMF on nuclear factor κB ligand (RANKL)-dependent osteoclastic differentiation and the Ca(2+)-calcineurin-NFATc1 signaling pathway in RAW264.7 cells in vitro. Treating RAW264.7 cells with RANKL for 4 days induced osteoclastic differentiation in vitro, and the formation of multinucleated osteoclasts, bone resorption-pit formation, tartrate-resistant acid phosphatase (TRAP) activity and the protein levels of cathepsin K, TRAP, Nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) and matrix metalloproteinase 9 (MMP-9) were significantly decreased...
January 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27836739/docosahexaenoic-acid-signaling-attenuates-the-proliferation-and-differentiation-of-bone-marrow-derived-osteoclast-precursors-and-promotes-apoptosis-in-mature-osteoclasts
#20
Hyun-Ju Kim, Boram Ohk, Hye Jin Yoon, Woo Youl Kang, Sook Jin Seong, Shin-Yoon Kim, Young-Ran Yoon
Docosahexaenoic acid (DHA), a component of omega-3 fatty acids, has been reported to protect against inflammatory bone diseases such as osteoporosis and rheumatoid arthritis. However, its exact mechanism in bone resorbing cells has not been elucidated. In this study, we investigated the effects and the molecular mechanism of DHA on the proliferation, differentiation, and survival of osteoclast lineage cells using mouse bone marrow-derived macrophages (BMMs). DHA suppressed the macrophage colony-stimulating factor (M-CSF)-induced proliferation of osteoclast precursors, BMMs, in a dose-dependent manner...
January 2017: Cellular Signalling
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