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AMPK AND bone

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https://www.readbyqxmd.com/read/27917698/tetramethylpyrazine-protects-against-glucocorticoid-induced-apoptosis-by-promoting-autophagy-in-mesenchymal-stem-cells-and-improves-bone-mass-in-glucocorticoid-induced-osteoporosis-rats
#1
Long Wang, Hong-Yang Zhang, Bo Gao, Jun Shi, Qiang Huang, Yue-Hu Han, Ya-Qian Hu, Wei-Guang Lu, Zhuo-Jie Zhao, Bao-Hua Liu, Qiang Jie, Liu Yang, Zhuo-Jing Luo
Glucocorticoid-induced osteoporosis (GIOP) is a widespread clinical complication due to the common use of glucocorticoids. Excess glucocorticoids induce apoptosis of bone marrow-derived mesenchymal stem cells (BMSCs), which have been shown to play an increasingly important role in the pathogenesis and therapy of osteoporosis. Tetramethylpyrazine (TMP), an extract from one of the most recognized herbs in traditional Chinese medicine (Chuanxiong), has been reported to have anti-apoptotic properties. In this study, we tested whether TMP protects rat BMSCs following exposure to glucocorticoids in vitro and in vivo...
December 4, 2016: Stem Cells and Development
https://www.readbyqxmd.com/read/27913299/the-inhibitory-effect-of-beta-lapachone-on-rankl-induced-osteoclastogenesis
#2
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...
November 30, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27897419/exercise-restores-muscle-stem-cell-mobilization-regenerative-capacity-and-muscle-metabolic-alterations-via-adiponectin-adipor1-activation-in-samp10-mice
#3
Aiko Inoue, Xian Wu Cheng, Zhe Huang, Lina Hu, Ryosuke Kikuchi, Haiying Jiang, Limei Piao, Takeshi Sasaki, Kohji Itakura, Hongxian Wu, Guangxian Zhao, Yanna Lei, Guang Yang, Enbo Zhu, Xiang Li, Kohji Sato, Teruhiko Koike, Masafumi Kuzuya
BACKGROUND: Exercise train (ET) stimulates muscle response in pathological conditions, including aging. The molecular mechanisms by which exercise improves impaired adiponectin/adiponectin receptor 1 (AdipoR1)-related muscle actions associated with aging are poorly understood. Here we observed that in a senescence-accelerated mouse prone 10 (SAMP10) model, long-term ET modulated muscle-regenerative actions. METHODS: 25-week-old male SAMP10 mice were randomly assigned to the control and the ET (45 min/time, 3/week) groups for 4 months...
November 29, 2016: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/27856330/metformin-suppresses-adipogenesis-through-both-amp-activated-protein-kinase-ampk-dependent-and-ampk-independent-mechanisms
#4
Suet Ching Chen, Rebecca Brooks, Jessica Houskeeper, Shaun K Bremner, Julia Dunlop, Benoit Viollet, Pamela J Logan, Ian P Salt, S Faisal Ahmed, Stephen J Yarwood
People with Type 2 diabetes mellitus (T2DM) have reduced bone mineral density and an increased risk of fractures due to altered mesenchymal stem cell (MSC) differentiation in the bone marrow. This leads to a shift in the balance of differentiation away from bone formation (osteogenesis) in favour of fat cell development (adipogenesis). The commonly used anti-diabetic drug, metformin, activates the osteogenic transcription factor Runt-related transcription factor 2 (Runx2), which may suppress adipogenesis, leading to improved bone health...
November 14, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27812336/piperine-suppresses-pyroptosis-and-interleukin-1%C3%AE-release-upon-atp-triggering-and-bacterial-infection
#5
Yi-Dan Liang, Wen-Jing Bai, Chen-Guang Li, Li-Hui Xu, Hong-Xia Wei, Hao Pan, Xian-Hui He, Dong-Yun Ouyang
Piperine is a phytochemical present in black pepper (Piper nigrum Linn) and other related herbs, possessing a wide array of pharmacological activities including anti-inflammatory effects. Previously, we demonstrated that piperine has therapeutic effects on bacterial sepsis in mice, but the underlying mechanism has not been fully elucidated. In this study, we aimed to investigate the influences of piperine on pyroptosis in murine macrophages. The results showed that piperine dose-dependently inhibited ATP-induced pyroptosis, thereby suppressing interleukin-1β (IL-1β) or high mobility group box-1 protein (HMGB1) release in LPS-primed bone marrow-derived macrophages and J774A...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27799356/simvastatin-induced-apoptosis-in-osteosarcoma-cells-a-key-role-of-rhoa-ampk-p38-mapk-signaling-in-antitumor-activity
#6
Walied Kamel, Eiji Sugihara, Hiroyuki Nobusue, Sayaka Yamaguchi-Iwai, Nobuyuki Onishi, Kenta Maki, Yumi Fukuchi, Koichi Matsuo, Akihiro Muto, Hideyuki Saya, Takatsune Shimizu
Osteosarcoma is the most common type of primary bone tumor, novel therapeutic agents for which are urgently needed. To identify such agents, we screened a panel of approved drugs with a mouse model of osteosarcoma. The screen identified simvastatin, which inhibited the proliferation and migration of osteosarcoma cells in vitro. Simvastatin also induced apoptosis in osteosarcoma cells in a manner dependent on inhibition of the mevalonate biosynthetic pathway. It also disrupted the function of the small GTPase RhoA and induced activation of AMP-activated protein kinase (AMPK) and p38 mitogen-activated protein kinase (MAPK), with AMPK functioning upstream of p38 MAPK...
October 31, 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27761470/metformin-inhibits-advanced-glycation-end-products-induced-inflammatory-response-in-murine-macrophages-partly-through-ampk-activation-and-rage-nf%C3%AE%C2%BAb-pathway-suppression
#7
Zhong'e Zhou, Yong Tang, Xian Jin, Chengjun Chen, Yi Lu, Liang Liu, Chengxing Shen
Advanced glycation end products (AGEs) are major inflammatory mediators in diabetes, affecting atherosclerosis progression via macrophages. Metformin slows diabetic atherosclerosis progression through mechanisms that remain to be fully elucidated. The present study of murine bone marrow derived macrophages showed that (1) AGEs enhanced proinflammatory cytokines (interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α)) mRNA expression, RAGE expression, and NFκB activation; (2) metformin pretreatment inhibited AGEs effects and AGEs-induced cluster designation 86 (CD86) (M1 marker) expression, while promoting CD206 (M2 marker) surface expression and anti-inflammatory cytokine (IL-10) mRNA expression; and (3) the AMPK inhibitor, Compound C, attenuated metformin effects...
2016: Journal of Diabetes Research
https://www.readbyqxmd.com/read/27740628/hedgehog-signaling-in-bone-regulates-whole-body-energy-metabolism-through-a-bone-adipose-endocrine-relay-mediated-by-pthrp-and-adiponectin
#8
Xu Zhang, Qianni Cheng, Yixiang Wang, Po Sing Leung, Kinglun Kingston Mak
Bone plays a role in energy metabolism, but the interplay between bone and other organs in this process is not completely understood. Here, we show that upregulated Hh signaling in bones results in increased whole-body energy expenditure, white adipose tissue (WAT) browning, hypoglycemia and skeletal muscle atrophy. We found that Hh signaling induces PTHrP secretion from bones and causes WAT browning. Injection of PTHrP-neutralizing antibody attenuates WAT browning and improves the circulating blood glucose level while high-fat diet treatment only rescues hypoglycemia...
October 14, 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27733575/frontline-science-d1-dopaminergic-receptor-signaling-activates-the-ampk-bioenergetic-pathway-in-macrophages-and-alveolar-epithelial-cells-and-reduces-endotoxin-induced-ali
#9
Nathaniel B Bone, Zhongyu Liu, Jean-Francois Pittet, Jaroslaw W Zmijewski
Catecholamines, including β-adrenergic and dopaminergic neurotransmitters, have an essential role in regulating the "fight or flight" reflex and also affects immune cell proinflammatory action. However, little is known about whether catecholamines prevent dysfunction of metabolic pathways associated with inflammatory organ injury, including development of acute lung injury (ALI). We hypothesize that selected catecholamines may reduce metabolic alterations in LPS-stimulated macrophages and in the lungs of mice subjected to endotoxin-induced ALI, a situation characterized by diminished activity of AMP-activated protein kinase (AMPK)...
October 12, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27729807/cx-5461-induces-autophagy-and-inhibits-tumor-growth-via-mammalian-target-of-rapamycin-related-signaling-pathways-in-osteosarcoma
#10
Leiming Li, Yan Li, Jiansong Zhao, Shuli Fan, Liguo Wang, Xu Li
Osteosarcoma (OS) is the most common primary bone tumor, but molecular mechanisms of the disease have not been well understood, and treatment of metastatic OS remains a challenge. Rapid ribosomal RNA synthesis in cancer is transcribed by RNA polymerase I, which results in unbridled cell growth. The recent discovery of CX-5461, a selective RNA polymerase I inhibitor, exerted its inhibitory effect of ribosomal RNA synthesis and antiproliferative potency. Here, we demonstrate that CX-5461 induces G2 arrest in the cell cycle and expression of microtubule-associated protein 1 light chain 3 II isoform in OS cell lines...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27712936/gsk621-activates-ampk-signaling-to-inhibit-lps-induced-tnf%C3%AE-production
#11
Yong-Hong Wu, Quan Li, Ping Li
LPS stimulation in macrophages/monocytes induces TNFα production. We here tested the potential effect of GSK621, a novel AMP-activated protein kinase (AMPK) activator, against the process. In RAW264.7 macrophages, murine bone marrow-derived macrophages (BMDMs), and chronic obstructive pulmonary disease (COPD) patients' monocytes, GSK621 significantly inhibited LPS-induced TNFα protein secretion and mRNA synthesis. Inhibition of AMPK, through AMPKα shRNA knockdown or dominant negative mutation (T172A), almost abolished GSK621's suppression on TNFα in RAW264...
October 3, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27693382/effects-of-physical-exercise-on-myokines-expression-and-brown-adipose-like-phenotype-modulation-in-rats-fed-a-high-fat-diet
#12
Sílvia Rocha-Rodrigues, Amaia Rodríguez, Alexandra M Gouveia, Inês O Gonçalves, Sara Becerril, Beatriz Ramírez, Jorge Beleza, Gema Frühbeck, António Ascensão, José Magalhães
AIMS: Exercise-stimulated myokine secretion into circulation may be related with browning in white adipose tissue (WAT), representing a positive metabolic effect on whole-body fat mass. However, limited information is yet available regarding the impact of exercise on myokine-related modulation of adipocyte phenotype in WAT from obese rats. MAIN METHODS: Sprague-Dawley rats (n=60) were divided into sedentary and voluntary physical activity (VPA) groups and fed with standard (35kcal% fat) or high-fat (HFD, 71kcal% fat)-isoenergetic diets...
November 15, 2016: Life Sciences
https://www.readbyqxmd.com/read/27613501/a-current-view-of-perlecan-in-physiology-and-pathology-a-mosaic-of-functions
#13
Maria A Gubbiotti, Thomas Neill, Renato V Iozzo
Perlecan, a large basement membrane heparan sulfate proteoglycan, is expressed in a wide array of tissues where it regulates diverse cellular processes including bone formation, inflammation, cardiac development, and angiogenesis. Here we provide a contemporary review germane to the biology of perlecan encompassing its genetic regulation as well as an analysis of its modular protein structure as it pertains to function. As perlecan signaling from the extracellular matrix converges on master regulators of autophagy, including AMPK and mTOR, via a specific interaction with vascular endothelial growth factor receptor 2, we specifically focus on the mechanism of action of perlecan in autophagy and angiogenesis and contrast the role of endorepellin, the C-terminal fragment of perlecan, in these cellular and morphogenic events...
September 6, 2016: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/27609031/msp-is-a-negative-regulator-of-inflammation-and-lipogenesis-in-ex-vivo-models-of-non-alcoholic-steatohepatitis
#14
Dipanjan Chanda, Jieyi Li, Yvonne Oligschlaeger, Mike L J Jeurissen, Tom Houben, Sofie M A Walenbergh, Ronit Shiri-Sverdlov, Dietbert Neumann
Non-alcoholic steatohepatitis (NASH), a metabolic disorder consisting of steatosis and inflammation, is considered the hepatic equivalent of metabolic syndrome and can result in irreversible liver damage. Macrophage-stimulating protein (MSP) is a hepatokine that potentially has a beneficial role in hepatic lipid and glucose metabolism via the activation of AMP-activated protein kinase (AMPK). In the current study, we investigated the regulatory role of MSP in the development of inflammation and lipid metabolism in various NASH models, both in vitro and ex vivo...
September 9, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27602960/endothelin-1-promotes-epithelial-mesenchymal-transition-in-human-chondrosarcoma-cells-by-repressing-mir-300
#15
Min-Huan Wu, Pei-Han Huang, Mingli Hsieh, Chun-Hao Tsai, Hsien-Te Chen, Chih-Hsin Tang
Chondrosarcoma is a malignant tumor of mesenchymal origin predominantly composed of cartilage-producing cells. This type of bone cancer is extremely resistant to radiotherapy and chemotherapy. Surgical resection is the primary treatment, but is often difficult and not always practical for metastatic disease, so more effective treatments are needed. In particular, it would be helpful to identify molecular markers as targets for therapeutic intervention. Endothelin-1 (ET-1), a potent vasoconstrictor, has been shown to enhance chondrosarcoma angiogenesis and metastasis...
September 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27600753/liraglutide-attenuates-the-osteoblastic-differentiation-of-mc3t3%C3%A2-e1-cells-by-modulating-ampk-mtor-signaling
#16
Xiong-Ke Hu, Xin-Hua Yin, Hong-Qi Zhang, Chao-Feng Guo, Ming-Xing Tang
Liraglutide, a synthetic analogue of glucagon-like peptide‑1, is utilized in the treatment of type 2 diabetes and obesity. Liraglutide has been previously demonstrated to prevent osteoblastic differentiation of human vascular smooth muscle cells, resulting in the slowing of arterial calcification, however, its effect on bone formation remains unclear. The present study investigated the effect of liraglutide on osteoblastic differentiation using Alizarin Red S staining, and examined the molecular mechanisms underlying the regulatory effect by western blot analysis...
October 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27524625/a-functional-link-between-ampk-and-orexin-mediates-the-effect-of-bmp8b-on-energy-balance
#17
Luís Martins, Patricia Seoane-Collazo, Cristina Contreras, Ismael González-García, Noelia Martínez-Sánchez, Francisco González, Juan Zalvide, Rosalía Gallego, Carlos Diéguez, Rubén Nogueiras, Manuel Tena-Sempere, Miguel López
AMP-activated protein kinase (AMPK) in the ventromedial nucleus of the hypothalamus (VMH) and orexin (OX) in the lateral hypothalamic area (LHA) modulate brown adipose tissue (BAT) thermogenesis. However, whether these two molecular mechanisms act jointly or independently is unclear. Here, we show that the thermogenic effect of bone morphogenetic protein 8B (BMP8B) is mediated by the inhibition of AMPK in the VMH and the subsequent increase in OX signaling via the OX receptor 1 (OX1R). Accordingly, the thermogenic effect of BMP8B is totally absent in ox-null mice...
August 23, 2016: Cell Reports
https://www.readbyqxmd.com/read/27492225/from-the-cover-autophagy-induction-contributes-to-cadmium-toxicity-in-mesenchymal-stem-cells-via-ampk-foxo3a-becn1-signaling
#18
Min Yang, Huifeng Pi, Min Li, Shangcheng Xu, Lei Zhang, Jia Xie, Li Tian, Manyu Tu, Mindi He, Yonghui Lu, Zhengping Yu, Zhou Zhou
Mesenchymal stem cells (MSCs) are a valuable in vitro model for investigating the bone toxicity of cadmium (Cd). Autophagy has been proposed to play a pivotal role in Cd-mediated toxicity. The FOXO family proteins are important transcription factors that are essential to autophagy induction. This study investigated the role of autophagy in Cd-induced skeleton damage and its potential mechanism. We exposed MSCs to different concentrations of cadmium chloride (3.5, 7, and 14 μM) for 24 h. We demonstrated that Cd treatment increased autophagic flux, and inhibition of autophagic process using BENC1 gene silencing blocked Cd-induced cell death...
November 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/27418435/adiponectin-enhances-bone-marrow-mesenchymal-stem-cell-resistance-to-flow-shear-stress-through-amp-activated-protein-kinase-signaling
#19
Lin Zhao, Chongxi Fan, Yu Zhang, Yang Yang, Dongjin Wang, Chao Deng, Wei Hu, Zhiqiang Ma, Shuai Jiang, Shouyi Di, Zhigang Qin, Jianjun Lv, Yang Sun, Wei Yi
Adiponectin has been demonstrated to protect the cardiovascular system and bone marrow mesenchymal stem cells (BMSCs). However, it is unclear whether adiponectin can protect BMSCs against flow shear stress (FSS). In this study, our aim was to explore the effects of adiponectin on BMSCs and to explore the role of AMP-activated protein kinase (AMPK) signaling in this process. Shear stress significantly inhibits the survival and increases the apoptosis of BMSCs in an intensity-dependent manner. The expression levels of TGF-β, bFGF, VEGF, PDGF, and Bcl2 are simultaneously reduced, and the phosphorylation levels of AMPK and ACC, as well as the expression level of Bax, are increased...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27384322/ogg1-dependent-dna-repair-regulates-nlrp3-inflammasome-and-prevents-atherosclerosis
#20
Gantsetseg Tumurkhuu, Kenichi Shimada, Jargalsaikhan Dagvadorj, Timothy R Crother, Wenxuan Zhang, Daniel Luthringer, Roberta A Gottlieb, Shuang Chen, Moshe Arditi
RATIONALE: Activation of NLRP3 (nucleotide-binding domain and leucine-rich repeat pyrin domain containing 3) inflammasome-mediating interleukin (IL)-1β secretion has emerged as an important component of inflammatory processes in atherosclerosis. Mitochondrial DNA (mtDNA) damage is detrimental in atherosclerosis, and mitochondria are central regulators of the nucleotide-binding domain and leucine-rich repeat pyrin domain containing 3 inflammasome. Human atherosclerotic plaques express increased mtDNA damage...
September 2, 2016: Circulation Research
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