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Osteoclast reactive oxygen species calcium

Subhashis Pal, Kainat Khan, Shyamsundar Pal China, Monika Mittal, Konica Porwal, Richa Shrivastava, Isha Taneja, Zakir Hossain, Dhanaraju Mandalapu, Jiaur R Gayen, Muhammad Wahajuddin, Vishnu Lal Sharma, Arun K Trivedi, Sabyasachi Sanyal, Smrati Bhadauria, Madan M Godbole, Sushil K Gupta, Naibedya Chattopadhyay
The drug, theophylline is frequently used as an additive to medications for people suffering from chronic obstructive pulmonary diseases (COPD). We studied the effect of theophylline in bone cells, skeleton and parameters related to systemic calcium homeostasis. Theophylline induced osteoblast apoptosis by increasing reactive oxygen species production that was caused by increased cAMP production. Bone marrow levels of theophylline were higher than its serum levels, indicating skeletal accumulation of this drug...
March 15, 2016: Toxicology and Applied Pharmacology
C Dou, Y Chen, N Ding, N Li, H Jiang, C Zhao, F Kang, Z Cao, H Quan, F Luo, J Xu, S Dong
UNLABELLED: Xanthotoxin (XAT) is extracted from the seeds of Ammi majus. Here, we reported that XAT has an inhibitory effect on osteoclastogenesis in vitro through the suppression of both receptor activator of nuclear factor-κB ligand (RANKL)-induced ROS generation and Ca(2+) oscillations. In vivo studies showed that XAT treatment decreases the osteoclast number, prevents bone loss, and restores bone strength in ovariectomized mice. INTRODUCTION: Excessive osteoclast formation and the resultant increase in bone resorption activity are key pathogenic factors of osteoporosis...
July 2016: Osteoporosis International
Ke Ke, M A Safder, Ok-Joo Sul, Woon-Ki Kim, Jae-Hee Suh, Yeonsoo Joe, Hun-Taeg Chung, Hye-Seon Choi
Heme oxygenase-1 (HO-1) has long been considered to be an endogenous antioxidant. However, the role of HO-1 is highly controversial in developing metabolic diseases. We hypothesized that HO-1 plays a role in maintaining bone mass by alleviating a redox imbalance. We investigated its role in bone remodeling. The absence of HO-1 in mice led to decreased bone mass with elevated activity and number of OCs, as well as higher serum levels of reactive oxygen species (ROS). HO-1, which is constitutively expressed at a high level in osteoclast (OC) precursors, was down-regulated during OC differentiation...
July 5, 2015: Molecular and Cellular Endocrinology
Jian Zhou, Shiqiao Ye, Toshifumi Fujiwara, Stavros C Manolagas, Haibo Zhao
Iron is essential for osteoclast differentiation, and iron overload in a variety of hematologic diseases is associated with excessive bone resorption. Iron uptake by osteoclast precursors via the transferrin cycle increases mitochondrial biogenesis, reactive oxygen species production, and activation of cAMP response element-binding protein, a critical transcription factor downstream of receptor activator of NF-κB-ligand-induced calcium signaling. These changes are required for the differentiation of osteoclast precursors to mature bone-resorbing osteoclasts...
October 18, 2013: Journal of Biological Chemistry
Jin-Kang Zhang, Liu Yang, Guo-Lin Meng, Zhi Yuan, Jing Fan, Dan Li, Jian-Zong Chen, Tian-Yao Shi, Hui-Min Hu, Bo-Yuan Wei, Zhuo-Jing Luo, Jian Liu
Oxidative stress is a pivotal pathogenic factor for bone loss in mouse model. Salidroside, a phenylpropanoid glycoside extracted from Rhodiola rosea L, exhibits potent antioxidative effects. In the present study, we used an in vitro oxidative stress model induced by hydrogen peroxide (H(2)O(2)) in MC3T3-E1 cells and a murine ovariectomized (OVX) osteoporosis model to investigate the protective effects of salidroside on bone loss and the related mechanisms. We demonstrated that salidroside caused a significant (P<0...
2013: PloS One
Hyunsoo Kim, Taesoo Kim, Byung-Chul Jeong, Il-Taeg Cho, Daehee Han, Noriko Takegahara, Takako Negishi-Koga, Hiroshi Takayanagi, Jae Hee Lee, Jai-Yoon Sul, Vikram Prasad, Seoung Hoon Lee, Yongwon Choi
Osteoclast maturation and function primarily depend on receptor activator of NF-κB ligand (RANKL)-mediated induction of nuclear factor of activated T cells c1 (NFATc1), which is further activated via increased intracellular calcium ([Ca(2+)](i)) oscillation. However, the coordination mechanism that mediates Ca(2+) oscillation during osteoclastogenesis remains ill defined. Here, we identified transmembrane protein 64 (Tmem64) as a regulator of Ca(2+) oscillation during osteoclastogenesis. We found that Tmem64-deficient mice exhibit increased bone mass due in part to impaired osteoclast formation...
February 5, 2013: Cell Metabolism
Lin Xia, Dongyan Zhang, Chune Wang, Fengcai Wei, Yingwei Hu
The precise mechanism of how TNF-α promotes osteoclast formation is not clear. Previous reports show TNF-α targets molecules that regulate calcium signaling. Inositol-1,4,5-trisphosphate receptors (IP3Rs) are important calcium channel responsible for evoking intracellular calcium oscillation. We found that TNF-α increased the expression of IP3R1 and promoted osteoclastogenesis in RANKL-induced mouse BMMs. Phosphatidylcholine-specific phospholipase C (PC-PLC) specific inhibitor D609 eliminated the upregulation of IP3R1 by TNF-α, and decreased the autoamplification of nuclear factor of activated T-cells 1 (NFATc1), thus resulted in less osteoclasts formation...
September 21, 2012: FEBS Letters
Yun Zhang, Ming Yan, Aiyue Yu, Hongjiao Mao, Jinping Zhang
Wear debris-induced osteolysis, a major contributing factor of orthopedic implant aseptic loosening, affects long-term survival of orthopedic prostheses following joint replacement and revision surgery. Pathogenic effects of wear debris on various cell types including macrophages/monocytes, osteoblasts, and osteoclasts have been well studied. However, the interactions between wear debris particles and osteocytes, which make up over 90% of all bone cells, have not been clearly illustrated. Here, we explored the biological effects of endotoxin-free beta-tricalciumphosphate (β-TCP) wear particles with the average diameter of 1...
July 16, 2012: Toxicology
Eun Mi Choi
Liquiritigenin is one of the flavonoids present in Glycyrrhizae radix. In the present study, the effects of liquiritigenin on the function of osteoblastic MC3T3-E1 cells were studied. Liquiritigenin caused a significant elevation of cell growth, alkaline phosphatase activity, collagen synthesis, mineralization, and glutathione content in the cells (P<0.05). Moreover, liquiritigenin significantly decreased the production of reactive oxygen species (ROS) and osteoclast differentiation inducing factors such as tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and receptor activator of nuclear factor-κB ligand (RANKL) in the presence of antimycin A, which inhibits mitochondrial electron transport and has been used as a ROS generator...
January 2012: International Immunopharmacology
Young Soon Lee, Eun Mi Choi
Apocynin is a naturally occurring methoxy-substituted catechol, experimentally used as an inhibitor of NADPH-oxidase. In the present study, the effect of apocynin on the function of osteoblastic MC3T3-E1 cells was studied. Apocynin caused a significant elevation of alkaline phosphatase (ALP) activity, collagen content, and mineralization in the cells (P<0.05). Antimycin A (AMA), which inhibits complex III of the electron transport system, has been used as a reactive oxygen species (ROS) generator in biological systems...
2011: Cellular Immunology
Min Seuk Kim, Yu-Mi Yang, Aran Son, Yu Shun Tian, Syng-Ill Lee, Sang Won Kang, Shmuel Muallem, Dong Min Shin
RANKL (receptor activator of NF-kappaB ligand) induces osteoclastogenesis by activating multiple signaling pathways in osteoclast precursor cells, chief among which is induction of long lasting oscillations in the intracellular concentration of Ca(2+) ([Ca(2+)](i)). The [Ca(2+)](i) oscillations activate calcineurin, which activates the transcription factor NFATc1. The pathway by which RANKL induces [Ca(2+)](i) oscillations and osteoclastogenesis is poorly understood. Here we report the discovery of a novel pathway induced by RANKL to cause a long lasting increase in reactive oxygen species (ROS) and [Ca(2+)](i) oscillations that is essential for differentiation of bone marrow-derived monocytes into osteoclasts...
March 5, 2010: Journal of Biological Chemistry
Eun Mi Choi, Gun-Hee Kim, Yong Soo Lee
Treatment of various types of cells with the mitochondrial ATP-sensitive K+ channel (mK(ATP)) opener has been shown to precondition cells to subsequent injuries and inhibit apoptosis. We exposed cultured osteoblastic MC3T3-E1 cells to hydrogen peroxide (H2O2) with or without pretreatment with a mK(ATP) opener, diazoxide. A marked decrease in osteoblast viability was evident after 48 h exposure of 0.3mM H2O2, compared with vehicle-treated cells. Diazoxide (0.001 approximately 10 microM) treatment significantly (P<0...
December 10, 2009: European Journal of Pharmacology
G David Roodman
Osteoclasts are the primary cells that resorb bone; they require high energy levels to degrade bone matrix, releasing minerals to maintain calcium homeostasis. Recent work on osteoclast differentiation and activity highlights an important role for mitochondrial biogenesis and explores the role of iron transferrin in generating a positive osteoclastogenic feedback loop.
May 2009: Cell Metabolism
Hideyuki Sasaki, Hironori Yamamoto, Kumiko Tominaga, Kiyoshi Masuda, Tomoko Kawai, Shigetada Teshima-Kondo, Kazuhito Rokutan
Reactive oxygen species (ROS) derived from NADPH oxidase (Nox) homologues have been suggested to regulate osteoclast differentiation. However, no bone abnormalities have been documented in Nox1 deficient, Nox2 deficient, or Nox3 mutant mice. During receptor activator of nuclear factor-kappaB ligand (RANKL)-stimulated differentiation of a mouse macrophage cell line (RAW264.7) into osteoclasts, mRNA levels of Nox enzymes (Nox1-4) and their adaptor proteins were monitored by real-time reverse transcriptase PCR...
February 2009: Journal of Medical Investigation: JMI
María Virginia Gangoiti, Ana María Cortizo, Verónica Arnol, Juan Ignacio Felice, Antonio Desmond McCarthy
Patients with long-standing Diabetes mellitus can develop osteopenia and osteoporosis. We have previously shown that advanced glycation endproducts reduce the bone-forming activity of osteoblasts. Bisphosphonates are used for the treatment of various bone disorders, since they reduce osteoclastic function and survival, and stimulate osteoblastic bone-forming capacity. In this work we have investigated whether bisphosphonates are able to revert advanced glycation endproducts-induced deleterious effects in osteoblasts...
December 14, 2008: European Journal of Pharmacology
Marcel Liberman, Estêvão Bassi, Marina Kamla Martinatti, Fábio Cerqueira Lario, João Wosniak, Pablo M A Pomerantzeff, Francisco R M Laurindo
OBJECTIVE: We hypothesized that reactive oxygen species (ROS) contribute to progression of aortic valve (AV) calcification/stenosis. METHODS AND RESULTS: We investigated ROS production and effects of antioxidants tempol and lipoic acid (LA) in calcification progression in rabbits given 0.5% cholesterol diet +10(4) IU/d Vit.D2 for 12 weeks. Superoxide and H2O2 microfluorotopography and 3-nitrotyrosine immunoreactivity showed increased signals not only in macrophages but preferentially around calcifying foci, in cells expressing osteoblast/osteoclast, but not macrophage markers...
March 2008: Arteriosclerosis, Thrombosis, and Vascular Biology
Satish Srinivasan, Narayan G Avadhani
Previously we showed that mitochondrial dysfunction induced by mitochondrial DNA depletion or treatment with electron transport chain inhibitors triggers a stress signaling involving activation of calcineurin and Ca2+-responsive factors. In this study we show that exposure of RAW 264.7 cells to hypoxia, causing increased reactive oxygen species (ROS) production and disruption of mitochondrial transmembrane potential, also induced a similar stress signaling. Hypoxia caused increased [Ca2+]c, activation of cytosolic calcineurin and induced expression of Ryanodine Receptor 2 (RyR2) gene...
November 2007: Annals of the New York Academy of Sciences
S A Sheweita, K I Khoshhal
Calcium ion is an essential structural component of the skeleton. There is growing evidence for the importance of nutrition in the maintenance of bones and joints health. Nutritional imbalance combined with endocrine abnormalities may be involved in osteoporosis. For example, essential fatty acids and their metabolites were reported to have beneficial action in osteoporosis. The mechanism by which fatty acids prevent osteoporosis may involve inhibition of pro-inflammatory cytokines, which are known to have a major role in osteoporosis through induction of oxidative stress which had adverse effects on the skeleton...
June 2007: Current Drug Metabolism
Nobuyuki Matsushima, Noritaka Nakamichi, Yuki Kambe, Katsura Takano, Nobuaki Moriguchi, Yukio Yoneda
We have previously shown that particular phenolic antidiarrheic ingredients, including 2-methoxy-4-methylphenol (2M4MP) and 2-methoxy-4-ethyphenol (2M4EP), but not 2-methoxyphenol (2MP), significantly inhibit cellular maturation and differentiation of the bone-resorbing osteoclasts with concomitant protection of the bone-forming osteoblasts against oxidative stress by hydrogen peroxide (H(2)O(2)). In the present study, we evaluated the pharmacological actions of these three major phenolic antidiarrheic ingredients on the cellular viability in cultured astrocytes and neurons of the rat brain in vitro...
July 12, 2007: European Journal of Pharmacology
Ilka Nemere, Cody Wilson, Wendy Jensen, Marla Steinbeck, Ben Rohe, Mary C Farach-Carson
In intestine, 24,25(OH)(2)D(3), which is made under conditions of calcium-, phosphate-, and 1,25(OH)(2)D(3) sufficiency, inhibits the stimulatory actions of 1,25(OH)(2)D(3) on phosphate and calcium absorption. In the current work, we provide evidence that 24,25(OH)(2)D(3)-mediated signal transduction occurs mechanistically through increased H(2)O(2) production which involves binding of 24,25(OH)(2)D(3) to catalase and resultant decreases in enzyme activity. Physiological levels of H(2)O(2) mimicked the action of 24,25(OH)(2)D(3) on inhibiting 1,25(OH)(2)D(3)-stimulated phosphate uptake in isolated enterocytes...
December 15, 2006: Journal of Cellular Biochemistry
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