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AMPK AND bone

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https://www.readbyqxmd.com/read/28213588/a-differential-autophagy-dependent-response-to-dna-double-strand-brakes-in-bone-marrow-mesenchymal-stem-cells-from-sporadic-als-patients
#1
Shane Wald-Altman, Edward Pichinuk, Or Kakhlon, Miguel Weil
Amyotrophic Lateral Sclerosis (ALS) is an incurable motor neurodegenerative disease caused by a diversity of genetic and environmental factors leading to neuromuscular degeneration and pathophysiological implications in non-neural systems. Our previous work showed abnormal transcriptional expression levels of biomarker genes in non-neuronal cell samples from ALS patients. The same genes proved to be differentially expressed in brain, spinal cord and muscle of the SOD1(G93A) ALS mouse model. These observations support the pathophysiological relevance of the ALS biomarkers discovered in human mesenchymal stem cells (hMSC) isolated from bone marrow samples of ALS patients (ALS-hMSC)...
February 16, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28198538/role-of-pin1-on-in-vivo-periodontal-tissue-and-in-vitro-cells
#2
K-H Park, E-H Cho, W-J Bae, H-S Kim, H-C Lim, Y-D Park, M-O Lee, E-S Cho, E-C Kim
BACKGROUND: Although expression of peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (PIN1) was reported in bone tissue, the precise role of PIN1 in periodontal tissue and cells remain unclear. MATERIAL & METHODS: To elucidate the roles of PIN1 in periodontal tissue, its expression in periodontal tissue and cells, and effects on in vitro 4 osteoblast differentiation and the underlying signaling mechanisms were evaluated. RESULTS: PIN1 was expressed in mouse periodontal tissues including periodontal ligament cells (PDLCs), cementoblasts and osteoblasts at the developing root formation stage (postnatal, PN14) and functional stage of tooth (PN28)...
February 15, 2017: Journal of Periodontal Research
https://www.readbyqxmd.com/read/28189115/n-3-polyunsaturated-fatty-acids-alleviate-high-glucose-mediated-dysfunction-of-endothelial-progenitor-cells-and-prevent-ischemic-injuries-both-in-vitro-and-in-vivo
#3
Shao-Chih Chiu, Che-Yi Chao, En-Pei Isabel Chiang, Jia-Ning Syu, Raymond L Rodriguez, Feng-Yao Tang
Hyperglycemia is associated with a reduced number of endothelial progenitor cells (EPCs) that impairs vascular function. Circulating EPCs play important roles in postnatal neovasculogenesis and the prevention of ischemic injury. Frequent consumption of fish oil (FO) that is abundant with eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) is reportedly associated with an alleviation of diabetic complications and a lowered incidence of cardiovascular disease. The aim of this study was to examine whether N-3 polyunsaturated fatty acids such as EPA and DHA would reverse the high glucose-mediated dysfunction of EPCs in vitro and thereby prevent the ischemic injury that occurs under the hyperglycemic conditions in Type 2 diabetes (T2D) db(-/-) mice...
January 28, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28176455/adiponectin-promotes-human-jaw-bone-marrow-mesenchymal-stem-cell-chemotaxis-via-cxcl1-and-cxcl8
#4
Yinfei Pu, Mengke Wang, Yingying Hong, Yuwei Wu, Zhihui Tang
Adiponectin (APN) is known to promote the osteogenic differentiation of human jaw bone marrow mesenchymal stem cells (h-JBMMSCs). However, the underlying mechanism has not been fully elucidated. Previously, we showed that APN could promote h-JBMMSC osteogenesis via APPL1-p38 by up-regulating osteogenesis-related genes. Here, we aimed to determine whether APN could promote h-JBMMSC chemotaxis through CXCL1/CXCL8. The CCK-8, wound healing and transwell assays were used to evaluate the proliferation, migration and chemotaxis of h-JBMMSCs with or without APN treatment...
February 8, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28108519/survival-of-acute-monocytic-leukemia-cells-is-driven-by-fatty-acid-oxidation-mediated-activation-of-ampk-in-bone-marrow-adipocytes
#5
Yoko Tabe, Shinichi Yamamoto, Kaori Saitoh, Kazumasa Sekihara, Norikazu Monma, Kazuho Ikeo, Kaoru Mogushi, Masato Shikami, Vivian R Ruvolo, Jo Ishizawa, Numsen Hail, Saiko Kazuno, Mamoru Igarashi, Hiromichi Matsushita, Yasunari Yamanaka, Hajime Arai, Isao Nagaoka, Takashi Miida, Yoshihide Hayashizaki, Marina Konopleva, Michael Andreeff
Leukemia cells in the bone marrow (BM) must meet the biochemical demands of increased cell proliferation by continually adapting to fluctuations in nutrient and oxygen availability. Thus, targeting metabolic abnormalities in leukemia cells located in the BM may provide an effective therapeutic strategy. In this study, we report the discovery of a metabolic role for BM adipocytes in supporting the growth of leukemic blasts. Preventing nutrient starvation-induced apoptosis of leukemic cells by BM adipocytes, as well as the metabolic and molecular mechanisms involved in this process, were investigated using various analytical techniques...
January 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28063979/calcium-phosphate-phosphorylated-adenosine-hybrid-microspheres-for-anti-osteosarcoma-drug-delivery-and-osteogenic-differentiation
#6
Zi-Fei Zhou, Tuan-Wei Sun, Feng Chen, Dong-Qing Zuo, Hong-Sheng Wang, Ying-Qi Hua, Zheng-Dong Cai, Jun Tan
Biocompatibility, biodegradability and bioactivity are significantly important in practical applications of various biomaterials for bone tissue engineering. Herein, we develop a functional inorganic-organic hybrid system of calcium phosphate-phosphorylated adenosine (CPPA). Both calcium phosphate and phosphorylated adenosine molecules in CPPA are fundamental components in mammalians and play important roles in biological metabolism. In this work, we report our three leading research qualities: (1) CPPA hybrid microspheres with hollow and porous structure are synthesized by a facile one-step microwave-assisted solvothermal method; (2) CPPA hybrid microspheres show high doxorubicin loading capacity and pH-responsive drug release properties, and demonstrate positive therapeutic effects on six osteosarcoma cell lines in vitro and a mouse model of 143B osteosarcoma subcutaneous tumor in vivo; (3) CPPA hybrid microspheres are favorable to promote osteogenic differentiation of human bone mesenchymal stem cells (hBMSCs) by activating the AMPK pathway, with satisfactory evidences from cellular alkaline phosphatase staining, alizarin red staining, real time PCR and western analysis...
March 2017: Biomaterials
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
#7
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
#8
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/27897419/exercise-restores-muscle-stem-cell-mobilization-regenerative-capacity-and-muscle-metabolic-alterations-via-adiponectin-adipor1-activation-in-samp10-mice
#9
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
#10
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...
January 15, 2017: 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
#11
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
#12
Walied A 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 MAPK, with AMPK functioning upstream of p38 MAPK...
January 2017: 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
#13
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
#14
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...
February 2017: 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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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