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https://www.readbyqxmd.com/read/28724617/human-venous-valve-disease-caused-by-mutations-in-foxc2-and-gjc2
#1
Oliver Lyons, Prakash Saha, Christopher Seet, Adam Kuchta, Andrew Arnold, Steven Grover, Victoria Rashbrook, Amélie Sabine, Gema Vizcay-Barrena, Ash Patel, Francesca Ludwinski, Soundrie Padayachee, Tsutomu Kume, Brenda R Kwak, Glen Brice, Sahar Mansour, Pia Ostergaard, Peter Mortimer, Steve Jeffery, Nigel Brown, Taija Makinen, Tatiana V Petrova, Bijan Modarai, Alberto Smith
Venous valves (VVs) prevent venous hypertension and ulceration. We report that FOXC2 and GJC2 mutations are associated with reduced VV number and length. In mice, early VV formation is marked by elongation and reorientation ("organization") of Prox1(hi) endothelial cells by postnatal day 0. The expression of the transcription factors Foxc2 and Nfatc1 and the gap junction proteins Gjc2, Gja1, and Gja4 were temporospatially regulated during this process. Foxc2 and Nfatc1 were coexpressed at P0, and combined Foxc2 deletion with calcineurin-Nfat inhibition disrupted early Prox1(hi) endothelial organization, suggesting cooperative Foxc2-Nfatc1 patterning of these events...
July 19, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28724396/pathogenic-roles-of-cxcl10-signaling-through-cxcr3-and-tlr4-in-macrophages-and-t-cells-relevance-for-arthritis
#2
Jong-Ho Lee, Bongjun Kim, Won Jong Jin, Hong-Hee Kim, Hyunil Ha, Zang Hee Lee
BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by uncontrolled joint inflammation and destruction of bone and cartilage. We previously reported that C-X-C motif chemokine 10 (CXCL10; also called IP-10) has important roles in joint inflammation and bone destruction in arthritis. However, the specific mechanisms by which CXCL10 regulates the recruitment of inflammatory cells and the production of osteoclastogenic cytokines in RA progression are not fully understood...
July 19, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28713268/sitagliptin-an-anti-diabetic-drug-suppresses-estrogen-deficiency-induced-osteoporosisin-vivo-and-inhibits-rankl-induced-osteoclast-formation-and-bone-resorption-in-vitro
#3
Chuandong Wang, Fei Xiao, Xinhua Qu, Zanjing Zhai, Guoli Hu, Xiaodong Chen, Xiaoling Zhang
Postmenopausal osteoporosis is a disease characterized by excessive osteoclastic bone resorption. Some anti-diabetic drugs were demonstrated for anti-osteoclastic bone-loss effects. The present study investigated the skeletal effects of chronic administration of sitagliptin, a dipeptidyl peptidase IV (DPP IV) inhibitor that is increasingly used for type 2 diabetes treatments, in an estrogen deficiency-induced osteoporosis and elucidated the associated mechanisms. This study indicated that sitagliptin effectively prevented ovariectomy-induced bone loss and reduced osteoclast numbers in vivo...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28708287/regulation-of-rankl-induced-osteoclastogenesis-by-ring-finger-protein-rnf114
#4
Boren Lin, Qi Ke, Douglas W Leaman, Vijay Goel, Anand Agarwal
Normal bone remodeling is a continuous process orchestrated by bone-resorbing osteoclasts and bone-forming osteoblasts, which an imbalance in bone remodeling results in metabolic bone diseases. RANKL, a member of the TNF cytokine family, functions as a key stimulator for osteoclast differentiation and maturation. Here, we report that RNF114, previously identified as a psoriasis susceptibility gene, plays a regulatory role in the RANKL/RANK/TRAF6 signaling pathway that mediates osteoclastogenesis. Our results demonstrated that RNF114 expression was significantly down-regulated in mouse osteoclast precursor cells undergoing RANKL-induced osteoclast differentiation...
July 14, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28690843/the-role-of-pd-1-in-regulation-of-macrophage-apoptosis-and-its-subversion-by-leishmania-donovani
#5
Shalini Roy, Purnima Gupta, Shreyasi Palit, Moumita Basu, Anindita Ukil, Pijush K Das
Programmed death-1 receptor (PD-1) expressed in many immune cells is known to trigger T-cell exhaustion but the significance of macrophage-associated PD-1 in relevance to macrophage apoptosis is not known. This study is aimed to delineate whether PD-1 pathway has any role in eliciting macrophage apoptosis and, if so, then how the intra-macrophage parasite, Leishmania donovani modulates PD-1 pathway for protecting its niche. Resting macrophages when treated with H2O2 showed increased PD-1 expression and apoptosis, which was further enhanced on PD-1 agonist treatment...
May 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28681916/luteoloside-prevents-lipopolysaccharide-induced-osteolysis-and-suppresses-rankl-induced-osteoclastogenesis-through-attenuating-rankl-signaling-cascades
#6
Fangming Song, Chengming Wei, Lin Zhou, A N Qin, Mingli Yang, Jennifer Tickner, Yuanjiao Huang, Jinmin Zhao, Jiake Xu
Bone destruction or osteolysis marked by excessive osteoclastic bone resorption is a very common medical condition. Identification of agents that can effectively suppress excessive osteoclast formation and function is crucial for prevention and treatment of osteolytic conditions such as periprosthetic joint infection and periprosthetic loosening. Luteoloside, a flavonoid, is a natural bioactive compound with anti-inflammation and anti-tumor properties. However, the effect of Luteoloside on inflammation-induced osteolysis is unknown...
July 6, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28674855/carnosic-acid-attenuates-rankl-induced-oxidative-stress-and-osteoclastogenesis-via-induction-of-nrf2-and-suppression-of-nf-%C3%AE%C2%BAb-and-mapk-signalling
#7
Dinesh Thummuri, V G M Naidu, Pradip Chaudhari
Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a redox-sensitive transcription factor, which plays an important role in the cellular defense against oxidative stress by induction of anti-oxidant and cytoprotective enzymes. In the current study, we sought to investigate the osteoprotective effect of carnosic acid (CA), a phenolic (catecholic) diterpene. It is widely identified for its electrophilic nature under oxidative stress conditions and thus anticipated to counter osteoporosis by facilitation of Nrf2 signalling...
July 4, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28672947/peucedanum-japonicum-thunb-ethanol-extract-suppresses-rankl-mediated-osteoclastogenesis
#8
Jeong-Mi Kim, Munkhsoyol Erkhembaatar, Guem-San Lee, Jin-Hyun Lee, Eun-Mi Noh, Minok Lee, Hyun-Kyung Song, Choong Hun Lee, Kang-Beom Kwon, Min Seuk Kim, Young-Rae Lee
The constituents of Peucedanum japonicum Thunb. (PJ) exhibit biological and pharmacological activities, including anti-obesity, anti-oxidant and anti-allergic activities. The aim of the present study was to examine in vitro effects of PJ in RANKL-induced signaling pathways, which determine osteoclast differentiation. PJ ethanol extract (PEE) exhibited anti-osteoporotic activity by disrupting the phospholipase C (PLC)-Ca2+-c-Fos/cAMP response element-binding protein (CREB)-nuclear factor of activated T cells, cytoplasmic 1 (NFATc1) signaling pathway during osteoclastogenesis...
July 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28661042/cd11b-promotes-the-differentiation-of-osteoclasts-induced-by-rankl-through-the-spleen-tyrosine-kinase-signalling-pathway
#9
Guoxi Yang, Xiaoyong Chen, Zhao Yan, Qingsheng Zhu, Chongfei Yang
Macrophage surface antigen-1 (Mac-1, CD11b/CD18) has been implicated in the regulation of osteoclastogenesis. In the synovial tissues of patients with aseptic loosening after total hip replacement, CD11b was up-regulated, which indicated that CD11b is closely involved in osteolysis around the prosthesis. We found that CD11b, but not CD18, promoted osteoclast (OC) maturation. Here, we show CD11b up-regulated the levels of spleen tyrosine kinase (Syk), c-Fos and nuclear factor of activated T cells, cytoplasmic-1 (NFATc1), as well as the activity of extracellular-regulated kinase (Erk), and as a result, osteoclast precursors (OCPs) differentiated and became tartrate-resistant acid phosphatase (TRAP)-positive...
June 29, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28655771/p115-rhogef-activates-the-rac1-gtpase-signaling-cascade-in-mcp1-induced-vascular-smooth-muscle-cell-migration-and-proliferation
#10
Nikhlesh K Singh, Jagadeesh Janjanam, Gadiparthi N Rao
Although the involvement of Rho proteins in the pathogenesis of vascular diseases is well studied, little is known about the role of their upstream regulators, namely, the Rho guanine nucleotide exchange factors (RhoGEFs). Here, we sought to identify the RhoGEFs involved in monocyte chemotactic protein 1 (MCP1)-induced vascular wall remodeling. We found that among the RhoGEFs tested, MCP1 induced tyrosine phosphorylation of p115 RhoGEF but not of PDZ RhoGEF or LARG in human aortic smooth muscle cells (HASMCs)...
June 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28651235/alpinumisoflavone-inhibits-osteoclast-differentiation-and-exerts-anti-osteoporotic-effect-in-ovariectomized-mice
#11
Wei Cong, Chao Zhou, Jun Yin
Alpinumisoflavone (AIF), a naturally occurring flavonoid compound exacted from Derris eriocarpa, has been found to have a number of pharmacological activities. However, its role in bone disorder has not been investigated. The aim of this study is to evaluate the osteoprotective effect of AIF on ovariectomy-induced bone loss in mice model and related underlying mechanisms. Our study provides experimental evidence that AIF could regulate the remodeling process of bone and exert osteoprotective effect against ovariectomy-induced bone loss...
June 23, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28637314/dna-methylation-signatures-and-coagulation-factors-in-the-peripheral-blood-leucocytes-of-epithelial-ovarian-cancer
#12
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
#13
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
#14
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...
August 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28595951/sumoylation-regulates-the-transcriptional-activity-of-different-human-nfat-isoforms-in-neurons
#15
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...
July 13, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28587149/suppression-of-osteoclastogenesis-by-melatonin-a-melatonin-receptor-independent-action
#16
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
#17
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
#18
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
#19
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
#20
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
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