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AMPK AND bone

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https://www.readbyqxmd.com/read/28424584/hif-1%C3%AE-overexpression-improves-transplanted-bone-mesenchymal-stem-cells-survival-in-rat-mcao-stroke-model
#1
Bingke Lv, Feng Li, Jianbang Han, Jie Fang, Limin Xu, Chengmei Sun, Tian Hua, Zhongfei Zhang, Zhiming Feng, Xiaodan Jiang
Bone mesenchymal stem cells (BMSCs) death after transplantation is a serious obstacle impacting on the outcome of cell therapy for cerebral infarction. This study was aimed to investigate whether modification of BMSCs with hypoxia-inducible factor 1α (Hif-1α) could enhance the survival of the implanted BMSCs. BMSCs were isolated from Wistar rats, and were infected with Hif-1α-GFP lentiviral vector or Hif-1α siRNA. The modified BMSCs were exposed to oxygen-glucose deprivation (OGD) condition, cellular viability and apoptosis were then assessed...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28367764/formononetin-an-isoflavone-activates-amp-activated-protein-kinase-%C3%AE-catenin-signalling-to-inhibit-adipogenesis-and-rescues-c57bl-6-mice-from-high-fat-diet-induced-obesity-and-bone-loss
#2
Jyoti Gautam, Vikram Khedgikar, Priyanka Kushwaha, Dharmendra Choudhary, Geet Kumar Nagar, Kapil Dev, Preety Dixit, Divya Singh, Rakesh Maurya, Ritu Trivedi
Balance between adipocyte and osteoblast differentiation is the key link of disease progression in obesity and osteoporosis. We have previously reported that formononetin (FNT), an isoflavone extracted from Butea monosperma, stimulates osteoblast formation and protects against postmenopausal bone loss. The inverse relationship between osteoblasts and adipocytes prompted us to analyse the effect of FNT on adipogenesis and in vivo bone loss, triggered by high-fat diet (HFD)-induced obesity. The anti-obesity effect and mechanism of action of FNT was determined in 3T3-L1 cells and HFD-induced obese male mice...
March 2017: British Journal of Nutrition
https://www.readbyqxmd.com/read/28334504/redd1-deficiency-impairs-autophagy-and-mitochondrial-biogenesis-in-articular-cartilage-and-increases-the-severity-of-experimental-osteoarthritis
#3
Oscar Alvarez-Garcia, Tokio Matsuzaki, Merissa Olmer, Lars Plate, Jeffery W Kelly, Martin K Lotz
Objective REDD1 is an endogenous inhibitor of mTOR that regulates cellular stress responses. REDD1 expression is decreased in aged and osteoarthritis (OA) cartilage and it regulates mTOR signaling and autophagy in articular chondrocytes in vitro. The present study investigated the effects of REDD1 deletion in vivo using a mouse model of experimental OA. Methods Severity of OA was histologically assessed in 4-month-old wild-type and in Redd1(-/-) mice subjected to surgical destabilization of the medial meniscus (DMM)...
March 23, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28330873/amp-activated-protein-kinase-%C3%AE-1-promotes-atherogenesis-by-increasing-monocyte-to-macrophage-differentiation
#4
Miao Zhang, Huaiping Zhu, Ye Ding, Zhaoyu Liu, Zhejun Cai, Ming-Hui Zou
Monocyte-to-macrophage differentiation, which can be initiated by physiological or atherogenic factors, is a pivotal process in atherogenesis, a disorder in which monocytes adhere to endothelial cells and subsequently migrate into the sub-endothelial spaces, where they differentiate into macrophages and macrophage-derived foam cells and cause atherosclerotic lesions. However, the monocyte-differentiation signaling pathways that are activated by atherogenic factors are poorly defined. Here we report that the AMP- activated protein kinase (AMPK) α1 in monocytes promotes atherosclerosis by increasing monocyte differentiation and survival...
March 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28282788/berberine-inhibits-palmitate-induced-nlrp3-inflammasome-activation-by-triggering-autophagy-in-macrophages-a-new-mechanism-linking-berberine-to-insulin-resistance-improvement
#5
Hang Zhou, Lili Feng, Fang Xu, Yi Sun, Yuxiang Ma, Xiong Zhang, Hailiang Liu, Ge Xu, Xuefeng Wu, Yan Shen, Yang Sun, Xudong Wu, Qiang Xu
NLRP3 (Nod-like receptor family pyrin domain containing 3) inflammasome has been reported to contribute to obesity-induced inflammation and insulin resistance. However, there are few drugs targeting NLRP3 inflammasome for the treatment of insulin resistance. In the present study, we showed that berberine (BBR) significantly suppressed saturated fatty acid palmitate (PA)-induced NLRP3 inflammasome activation and interleukin-1β (IL-1β) release in macrophages, which was one of the most important mediators in the insulin sensitivity of adipose tissue...
March 6, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28235712/ampk-activation-reduces-the-number-of-atheromata-macrophages-in-apoe-deficient-mice
#6
Jing Wang, Ang Ma, Ming Zhao, Haibo Zhu
BACKGROUND AND AIMS: CC chemokine receptor 2 (Ccr2) governs migration of inflammatory Ly6C(hi) monocytes from the bone marrow (BM) to the circulating blood, which is a key step for macrophage accumulation during progression of atherosclerosis. Hyperlipidemia is often accompanied by low AMP-activated kinase (AMPK) activity and increased expression of Ccr2. The aim of this study was to examine whether there is a link between AMPK and chemokine networks. METHODS: ApoE(-/-) mice were fed a western diet and treated daily with AMPK activators (AICAR, A769662, or Metformin) or vehicle for 10 weeks...
March 2017: Atherosclerosis
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
#7
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
#8
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
#9
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
#10
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/bone-marrow-adipocytes-facilitate-fatty-acid-oxidation-activating-ampk-and-a-transcriptional-network-supporting-survival-of-acute-monocytic-leukemia-cells
#11
Yoko Tabe, Shinichi Yamamoto, Kaori Saitoh, Kazumasa Sekihara, Norikazu Monma, Kazuho Ikeo, Kaoru Mogushi, Masato Shikami, Vivian 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 must meet the biochemical demands of increased cell proliferation and also survive by continually adapting to fluctuations in nutrient and oxygen availability. Thus, targeting metabolic abnormalities in leukemia cells located in the bone marrow is a novel therapeutic approach. In this study, we investigated the metabolic role of bone marrow adipocytes in supporting the growth of leukemic blasts. Prevention of nutrient starvation-induced apoptosis of leukemic cells by bone marrow adipocytes, as well as the metabolic and molecular mechanisms involved in this process, was investigated using various analytic techniques...
March 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28063979/calcium-phosphate-phosphorylated-adenosine-hybrid-microspheres-for-anti-osteosarcoma-drug-delivery-and-osteogenic-differentiation
#12
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
#13
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 antiapoptotic properties. In this study, we tested whether TMP protects rat BMSCs following exposure to glucocorticoids in vitro and in vivo...
March 15, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/27913299/the-inhibitory-effect-of-beta-lapachone-on-rankl-induced-osteoclastogenesis
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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