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https://www.readbyqxmd.com/read/28637314/dna-methylation-signatures-and-coagulation-factors-in-the-peripheral-blood-leucocytes-of-epithelial-ovarian-cancer
#1
Lian Li, Hong Zheng, Yubei Huang, Caiyun Huang, Shuang Zhang, Jing Tian, Pei Li, Anil K Sood, Wei Zhang, Kexin Chen
Solid tumors are increasingly recognized as a systemic disease that is manifested by changes in DNA, RNA, proteins, and metabolites in the blood. Whereas many studies have reported gene mutation events in the circulation, few studies have focused on epigenetic DNA methylation markers. To identify DNA methylation biomarkers in peripheral blood for ovarian cancer, we performed a two-stage epigenome-wide association study. In the discovery stage, we measured genome wide DNA methylation for 485,000 CpG sites in peripheral blood in 24 epithelial ovarian cancer cases and 24 age-matched healthy controls...
June 16, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28637021/dectin-1-signaling-inhibits-osteoclastogenesis-via-il-33-induced-inhibition-of-nfatc1
#2
Xiaoqing Zhu, Yinghua Zhao, Yuxue Jiang, Tianxue Qin, Jintong Chen, Xiao Chu, Qing Yi, Sujun Gao, Siqing Wang
Abnormal osteoclast activation contributes to osteolytic bone diseases (OBDs). It was reported that curdlan, an agonist of dectin-1, inhibits osteoclastogenesis. However, the underlying mechanisms are not fully elucidated. In this study, we found that curdlan potently inhibited RANKL-induced osteoclast differentiation and the resultant bone resorption. Curdlan inhibited the expression of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), the key transcriptional factor for osteoclastogenesis. Notably, dectin-1 activation increased the expression of MafB, an inhibitor of NFATc1, and IL-33 in osteoclast precursors...
June 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28605877/ginsenoside-rb2-inhibits-osteoclast-differentiation-through-nuclear-factor-kappab-and-signal-transducer-and-activator-of-transcription-protein-3-signaling-pathway
#3
Fei Cong, Jian Liu, Chunmei Wang, Zhi Yuan, Long Bi, Jidong Liang, Ke Su, Yucheng Qiu, Tao Song, Jinzhu Fan, Gao Chao
Ginsenoside-Rb2 (Rb2) is a 20(S)-protopanaxadiol glycoside extracted from ginseng possessing various bioactivities which has drawn considerable interest regarding the area of bone metabolism. However, the effect of Rb2 on osteoclast differentiation remains unknown. In this study, we aimed to investigate the potential role of Rb2 in regulating osteoclast differentiation and the underlying molecular mechanisms. Osteoclast differentiation was induced by receptor activator nuclear factor-kappaB (NF-κB) ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) in mouse RAW 264...
June 8, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28595951/sumoylation-regulates-the-transcriptional-activity-of-different-human-nfat-isoforms-in-neurons
#4
Hanna Vihma, Tõnis Timmusk
In the nervous system, four calcium/calcineurin-regulated members of the nuclear factor of activated T-cells (NFAT) family of transcription factors, NFATc1-c4, are involved in many developmental and functional processes, such as corticogenesis, synaptogenesis, synaptic plasticity and neurotransmission, that all need precise gene regulation. Therefore it is important to understand molecular events that contribute to the regulation of the transcriptional activity of specific NFAT isoforms. Previously, we have shown that there are a number of alternative splice variants of NFAT genes expressed in the brain and that neuronal activity leads to isoform-specific transactivation capacities of different human NFAT proteins...
June 10, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28587149/suppression-of-osteoclastogenesis-by-melatonin-a-melatonin-receptor-independent-action
#5
Hyung Joon Kim, Ha Jin Kim, Moon-Kyoung Bae, Yong-Deok Kim
In vertebrates, melatonin is primarily secreted from the pineal gland but it affects various biological processes including the sleep-wake cycle, vasomotor control, immune system and bone homeostasis. Melatonin has been known to promote osteoblast differentiation and bone maturation, but a direct role of melatonin on osteoclast differentiation is still elusive. The present study investigated the effect of melatonin on the differentiation of macrophages to osteoclasts. The presence of melatonin significantly reduced receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclastogenesis and the siRNA-mediated knockdown of the melatonin receptor failed to overcome the anti-osteoclastogenic effect of melatonin...
May 26, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28581488/osteoblast-derived-laminin-332-is-a-novel-negative-regulator-of-osteoclastogenesis-in-bone-microenvironments
#6
Norihisa Uehara, Akiko Kukita, Yukari Kyumoto-Nakamura, Takayoshi Yamaza, Hisataka Yasuda, Toshio Kukita
Laminin-332 (Lm-332), a major basement membrane protein, has been shown to provide a niche for some stem cells. Here, we found that Lm-332 was expressed in osteoblasts, and is implicated in the regulation of osteoclast differentiation. Immunofluorescence analysis of laminin-β3, a unique component of Lm-332, indicated specific expression of laminin-β3 in osteoblast-like cells localized on bone surface. RT-PCR analysis confirmed that α3, β3, and γ2 chains of Lm-332 were all expressed in primary osteoblasts prepared from mouse calvaria...
June 5, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28575726/sciadopitysin-suppresses-rankl-mediated-osteoclastogenesis-and-prevents-bone-loss-in-lps-treated-mice
#7
Jinjin Cao, Qiang Lu, Ning Liu, Yu-Xin Zhang, Jing Wang, Maolin Zhang, Hong-Bing Wang, Wan-Chun Sun
Previous studies reported that sciadopitysin (Sc), a type of biflavonoids, protects reactive oxygen species (ROS)-mediated osteoblast dysfunction, but its role in osteoclastogenesis remains unclear. In this study, we observed that Sc dose-dependently suppressed RANKL-induced osteoclastogenesis and bone resorption. Our results indicated that Sc treatment strongly reduced RANKL-induced osteoclast-specific genes expression, including cathepsin K (CTSK), tartrate-resistant acid phosphatase (TRAP) and MMP-9. Furthermore, Sc apparently attenuated RANKL-increased expressions of c-Fos and NFATc1...
May 30, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28574596/g-protein-coupled-receptor-84-controls-osteoclastogenesis-through-inhibition-of-nf-%C3%AE%C2%BAb-and-mapk-signaling-pathways
#8
Ji-Wan Park, Hye-Jin Yoon, Woo Youl Kang, Seungil Cho, Sook Jin Seong, Hae Won Lee, Young-Ran Yoon, Hyun-Ju Kim
GPR84, a member of the G protein-coupled receptor family, is found predominantly in immune cells, such as macrophages, and functions as a pivotal modulator of inflammatory responses. In this study, we investigated the role of GPR84 in receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation. Our microarray data showed that GPR84 was significantly downregulated in osteoclasts compared to in their precursors, macrophages. The overexpression of GPR84 in bone marrow-derived macrophages suppressed the formation of multinucleated osteoclasts without affecting precursor proliferation...
June 2, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28570402/genetic-factors-involved-in-mandibular-prognathism
#9
Anna Doraczynska-Kowalik, Kamil H Nelke, Wojciech Pawlak, Maria M Sasiadek, Hanna Gerber
Mandibular prognathism is defined as an abnormal forward projection of the mandible beyond the standard relation to the cranial base and it is usually categorized as both a skeletal Class III pattern and Angle Class III malocclusion. The etiology of mandibular prognathism is still uncertain, with various genetic, epigenetic, and environmental factors possibly involved. However, many reports on its coexistence in both twins and segregation in families suggest the importance of genetic influences. A multifactorial and polygenic background with a threshold for expression or an autosomal dominant mode with incomplete penetrance and variable expressivity are the most probable inheritance patterns...
May 31, 2017: Journal of Craniofacial Surgery
https://www.readbyqxmd.com/read/28567098/barley-seedling-extracts-inhibit-rankl-induced-differentiation-fusion-and-maturation-of-osteoclasts-in-the-early-to-late-stages-of-osteoclastogenesis
#10
Sik-Won Choi, Shin-Hye Kim, Kwang-Sik Lee, Hyeon Jung Kang, Mi Ja Lee, Kie-In Park, Jin Hwan Lee, Ki Do Park, Woo Duck Seo
The number of patients with osteoporosis is increasing worldwide, and a decrease in bone mass is a main risk factor for fracture. The prevention of bone loss is critical for improving the quality of life for patients. However, the long-term use of antiosteoporotic agents is limited due to their side effects. Barley has been traditionally ingested for thousands of years as a safe, natural food with pharmaceutical properties, and its seedling can enhance the biological activity of the medicinal components found in food...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28545453/genome-wide-methylation-analysis-reveals-differentially-methylated-loci-that-are-associated-with-an-age-dependent-increase-in-bovine-fibroblast-response-to-lps
#11
Filiz T Korkmaz, David E Kerr
BACKGROUND: Differences in DNA methylation are known to contribute to the development of immune-related disorders in humans but relatively little is known about how methylation regulates immune function in cattle. Utilizing whole-transcriptome analyses of bovine dermal fibroblasts, we have previously identified an age and breed-dependent up-regulation of genes within the toll-like receptor 4 (TLR4) pathway that correlates with enhanced fibroblast production of IL-8 in response to lipopolysaccharide (LPS)...
May 25, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28543070/tnf-%C3%AE-has-both-stimulatory-and-inhibitory-effects-on-mouse-monocyte-derived-osteoclastogenesis
#12
Yixuan Cao, Ineke D C Jansen, Sara Sprangers, Teun J de Vries, Vincent Everts
Phenotypically different osteoclasts may be generated from different subsets of precursors. To what extent the formation of these osteoclasts is influenced or mediated by the inflammatory cytokine TNF-α, is unknown and was investigated in this study. The osteoclast precursors early blasts (CD31(hi) Ly-6C(-) ), myeloid blasts (CD31(+) Ly-6C(+) ) and monocytes (CD31(-) Ly-6C(hi) ) were sorted from mouse bone marrow using flow cytometry and cultured with M-CSF and RANKL, with or without TNF-α. Surprisingly, TNF-α prevented the differentiation of TRAcP(+) osteoclasts generated from monocytes on plastic; an effect not seen with early blasts and myeloid blasts...
May 20, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28539667/strontium-loaded-titania-nanotube-arrays-repress-osteoclast-differentiation-through-multiple-signalling-pathways-in-vitro-and-in-vivo-studies
#13
Baoguo Mi, Wei Xiong, Na Xu, Hanfeng Guan, Zhong Fang, Hui Liao, Yong Zhang, Biao Gao, Xiang Xiao, Jijiang Fu, Feng Li
The loosening of implants is an important clinical issue, particularly for patients with osteoporosis. In these patients, an implant should preferably both promote osteoblast differentiation and repress osteoclastic resorption. In the present study, we fabricated coatings containing TiO2 nanotubes (NTs) incorporated with strontium (Sr) on titanium (Ti) surfaces through hydrothermal treatment. The amount of loaded Sr was controlled by hydrothermally treating the samples in a Sr(OH)2 solution for 1 and 3 h (samples NT-Sr1h and NT-Sr3h, respectively) and found that both types of NT-Sr samples inhibited osteoclast differentiation by reducing the expression of osteoclast marker genes...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28530645/myc-dependent-oxidative-metabolism-regulates-osteoclastogenesis-via-nuclear-receptor-err%C3%AE
#14
Seyeon Bae, Min Joon Lee, Se Hwan Mun, Eugenia G Giannopoulou, Vladimir Yong-Gonzalez, Justin R Cross, Koichi Murata, Vincent Giguère, Marjolein van der Meulen, Kyung-Hyun Park-Min
Osteoporosis is a metabolic bone disorder associated with compromised bone strength and an increased risk of fracture. Inhibition of the differentiation of bone-resorbing osteoclasts is an effective strategy for the treatment of osteoporosis. Prior work by our laboratory and others has shown that MYC promotes osteoclastogenesis in vitro, but the underlying mechanisms are not well understood. In addition, the in vivo importance of osteoclast-expressed MYC in physiological and pathological bone loss is not known...
May 22, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28530641/the-many-ways-of-osteoclast-activation
#15
Joseph Lorenzo
Osteoclasts are the cells responsible for bone resorption, a process that is essential for the maintenance of healthy bones. Bone diseases, such as osteoporosis, which are characterized by high rates of bone resorption and loss of bone mass, may benefit from treatments that inhibit osteoclast formation and/or function. The RANKL/RANK pathway is critical for both osteoclast formation and function, and these effects are thought to be mediated by the transcription factor nuclear factor of activated T cells, cytoplasmic 1 (NFATc1)...
May 22, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28524179/a-fkbp5-mutation-is-associated-with-paget-s-disease-of-bone-and-enhances-osteoclastogenesis
#16
Bingru Lu, Yulian Jiao, Yinchang Wang, Jing Dong, Muyun Wei, Bin Cui, Yafang Sun, Laicheng Wang, Bingchang Zhang, Zijiang Chen, Yueran Zhao
Paget's disease of bone (PDB) is a common metabolic bone disease that is characterized by aberrant focal bone remodeling, which is caused by excessive osteoclastic bone resorption followed by disorganized osteoblastic bone formation. Genetic factors are a critical determinant of PDB pathogenesis, and several susceptibility genes and loci have been reported, including SQSTM1, TNFSF11A, TNFRSF11B, VCP, OPTN, CSF1 and DCSTAMP. Herein, we report a case of Chinese familial PDB without mutations in known genes and identify a novel c...
May 19, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28520214/mtorc1-inhibits-nf-%C3%AE%C2%BAb-nfatc1-signaling-and-prevents-osteoclast-precursor-differentiation-in-vitro-and-in-mice
#17
Yue Zhang, Song Xu, Kai Li, Kang Tan, Kangyan Liang, Jian Wang, Junhui Shen, Wenchong Zou, Le Hu, Daozhang Cai, Changhai Ding, Mangmang Li, Guozhi Xiao, Bin Liu, Anling Liu, Xiaochun Bai
The mechanistic target of rapamycin complex 1 (mTORC1) is a critical sensor for bone homeostasis and bone formation; however, the role of mTORC1 in osteoclast development and the underlying mechanisms have not yet been fully established. Here, we found that mTORC1 activity declined during osteoclast precursors differentiation in vitro and in vivo. We further targeted deletion of Raptor (mTORC1 key component) or Tsc1 (mTORC1 negative regulator) to constitutively inhibit or activate mTORC1 in osteoclast precursors (monocytes/macrophages), using LyzM-cre mice...
May 18, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28515152/effects-of-deficiency-of-kelch-like-ech-associated-protein-1-on-skeletal-organization-a-mechanism-for-diminished-nuclear-factor-of-activated-t-cells-cytoplasmic-1-during-osteoclastogenesis
#18
Eiko Sakai, Masanobu Morita, Masahiro Ohuchi, Mizuho A Kido, Yutaka Fukuma, Kazuhisa Nishishita, Kuniaki Okamoto, Ken Itoh, Masayuki Yamamoto, Takayuki Tsukuba
Kelch-like ECH-associated protein 1 (Keap1) binds to nuclear factor E2 p45-related factor 2 (Nrf2), a transcription factor for antioxidant enzymes, to suppress Nrf2 activation. The role of oxidative stress in many diseases supports the possibility that processes that are associated with Nrf2 activation might offer therapeutic potential. Nrf2 deficiency induces osteoclastogenesis, which is responsible for bone loss, by activating receptor activator of NF-κB ligand (RANKL)-mediated signaling; however, the effects of Keap1 deficiency remain unclear...
May 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28509877/human-beta-defensin-2-selectively-inhibits-hiv-1-in-highly-permissive-ccr6%C3%A2-%C2%BAcd4%C3%A2-%C2%BA-t-cells
#19
Mark K Lafferty, Lingling Sun, Aaron Christensen-Quick, Wuyuan Lu, Alfredo Garzino-Demo
Chemokine receptor type 6 (CCR6)⁺CD4⁺ T cells are preferentially infected and depleted during HIV disease progression, but are preserved in non-progressors. CCR6 is expressed on a heterogeneous population of memory CD4⁺ T cells that are critical to mucosal immunity. Preferential infection of these cells is associated, in part, with high surface expression of CCR5, CXCR4, and α4β7. In addition, CCR6⁺CD4⁺ T cells harbor elevated levels of integrated viral DNA and high levels of proliferation markers...
May 16, 2017: Viruses
https://www.readbyqxmd.com/read/28506889/nfam1-signaling-enhances-osteoclast-formation-and-bone-resorption-activity-in-paget-s-disease-of-bone
#20
Yuvaraj Sambandam, Kumaran Sundaram, Takamitsu Saigusa, Sundaravadivel Balasubramanian, Sakamuri V Reddy
Paget's disease of bone (PDB) is marked by the focal activity of abnormal osteoclasts (OCLs) with excess bone resorption. We previously detected measles virus nucleocapsid protein (MVNP) transcripts in OCLs from patients with PDB. Also, MVNP stimulates pagetic OCL formation in vitro and in vivo. However, the mechanism by which MVNP induces excess OCLs/bone resorption activity in PDB is unclear. Microarray analysis identified MVNP induction of NFAM1 (NFAT activating protein with ITAM motif 1) expression. Therefore, we hypothesize that MVNP induction of NFAM1 enhances OCL differentiation and bone resorption in PDB...
May 12, 2017: Bone
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