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https://www.readbyqxmd.com/read/28444839/age-dependent-alterations-in-osteoblast-and-osteoclast-activity-in-human-cancellous-bone
#1
Mustafa Becerikli, Henriette Jaurich, Jessica Schira, Matthias Schulte, Carmen Döbele, Christoph Wallner, Stephanie Abraham, Johannes M Wagner, Mehran Dadras, Ulrich Kneser, Marcus Lehnhardt, Björn Behr
It is assumed that the activity of osteoblasts and osteoclasts is decreased in bone tissue of aged individuals. However, detailed investigation of the molecular signature of human bone from young compared to aged individuals confirming this assumption is lacking. In this study, quantitative expression analysis of genes related to osteogenesis and osteoclastogenesis of human cancellous bone derived from the distal radius of young and aged individuals was performed. Furthermore, we additionally performed immunohistochemical stainings...
April 26, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28414795/negative-feedback-loop-of-bone-resorption-by-nfatc1-dependent-induction-of-cadm1
#2
Shinya Nakamura, Takuma Koyama, Naohiro Izawa, Seitaro Nomura, Takanori Fujita, Yasunori Omata, Takashi Minami, Morio Matsumoto, Masaya Nakamura, Eriko Fujita-Jimbo, Takashi Momoi, Takeshi Miyamoto, Hiroyuki Aburatani, Sakae Tanaka
Trimethylation of histone H3 lysine 4 and lysine 27 (H3K4me3 and H3K27me3) at gene promoter regions critically regulates gene expression. Key developmental genes tend to exhibit changes in histone modification patterns from the H3K4me3/H3K27me3 bivalent pattern to the H3K4me3 monovalent pattern. Using comprehensive chromatin immunoprecipitation followed by sequencing in bone marrow-derived macrophages (BMMs) and mature osteoclasts, we found that cell surface adhesion molecule 1 (Cadm1) is a direct target of nuclear factor of activated T cells 1 (NFATc1) and exhibits a bivalent histone pattern in BMMs and a monovalent pattern in osteoclasts...
2017: PloS One
https://www.readbyqxmd.com/read/28391779/tusc2-fus1-regulates-osteoclast-differentiation-through-nf-%C3%AE%C2%BAb-and-nfatc1
#3
Inyoung Kim, Jung Ha Kim, Kabsun Kim, Semun Seong, Nacksung Kim
Tumor suppressor candidate 2 (Tusc2, also known as Fus1) regulates calcium signaling, and Ca2+-dependent nuclear factor of activated T-cells (NFAT) and nuclear factor kappa B (NF-κB) pathways, which play roles in osteoclast differentiation. However, the role of Tusc2 in osteoclasts remains unknown. Here, we report that Tusc2 positively regulates the differentiation of osteoclasts. Overexpression of Tusc2 in osteoclast precursor cells enhanced receptor of nuclear factor κB ligand (RANKL)-induced osteoclast differentiation...
April 10, 2017: BMB Reports
https://www.readbyqxmd.com/read/28390147/concise-review-stem-cells-in-osteoimmunology
#4
Fernando A Fierro, Jan Nolta, Iannis E Adamopoulos
Bone remodeling is a lifelong process in which mature bone tissue is removed from the skeleton by bone resorption and is replenished by new during ossification or bone formation. The remodeling cycle requires both the differentiation and activation of two cell types with opposing functions. The osteoclast, which orchestrates bone resorption, and the osteoblast, which orchestrates bone formation. The differentiation of these cells from their respective precursors is a process which has been overshadowed by enigma, particularly because the precise osteoclast precursor has not been identified and because the identification of skeletal stem cells (SSC), which give rise to osteoblasts, is very recent...
April 8, 2017: Stem Cells
https://www.readbyqxmd.com/read/28378938/ag490-suppresses-interleukin-34-mediated-osteoclastogenesis-in-mice-bone-marrow-macrophages
#5
Xin Cheng, Qi-Long Wan, Zu-Bing Li
Interleukin-34 (IL-34) has been recently identified as a novel cytokine, substituting for the function of macrophage colony-stimulating factor (M-CSF), a pivotal osteoclastogenic factor involved in bone-related diseases (e.g., osteomyelitis of the jaws). However, the molecular mechanisms are not fully understood. This study aimed to explore the potential mechanism of IL-34 in receptor activator of NF-kB Ligand (RANKL)-induced osteoclast formation. We found that IL-34 alone significantly maintained the survival of bone-marrow macrophages (BMMs) and enhanced the expression of the osteoclast-related genes TRAP, Ctsk, and NFATc1, as well as TRAP-positive multinucleated cells combined with RANKL, which can be reversed by AG490...
April 5, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28374823/inhibitory-effects-of-dopamine-receptor-d1-agonist-on-mammary-tumor-and-bone-metastasis
#6
Kazumasa Minami, Shengzhi Liu, Yang Liu, Andy Chen, Qiaoqiao Wan, Sungsoo Na, Bai-Yan Li, Nariaki Matsuura, Masahiko Koizumi, Yukun Yin, Liangying Gan, Aihua Xu, Jiliang Li, Harikrishna Nakshatri, Hiroki Yokota
Dopaminergic signaling plays a critical role in the nervous system, but little is known about its potential role in breast cancer and bone metabolism. A screening of ~1,000 biologically active compounds revealed that a selective agonist of dopamine receptor D1 (DRD1), A77636, inhibited proliferation of 4T1.2 mammary tumor cells as well as MDA-MB-231 breast cancer cells. Herein, we examined the effect of A77636 on bone quality using a mouse model of bone metastasis from mammary tumor. A77636 inhibited migration of cancer cells in a DRD1-dependent fashion and suppressed development of bone-resorbing osteoclasts by downregulating NFATc1 through the elevation of phosphorylation of eIF2α...
April 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28370465/pharmacologic-calcitriol-inhibits-osteoclast-lineage-commitment-via-the-bmp-smad1-i%C3%AE%C2%BAb-nf-%C3%AE%C2%BAb-pathway
#7
Anna Li, Qian Cong, Xuechun Xia, Wai Fook Leong, James Yeh, Dengshun Miao, Yuji Mishina, Huijuan Liu, Baojie Li
Vitamin D is involved in a range of physiological processes and its active form and analogs have been used to treat diseases such as osteoporosis. Yet how vitamin D executes its function remains unsolved. Here we show that the active form of vitamin D calcitriol increases the peak bone mass in mice by inhibiting osteoclastogenesis and bone resorption. Although calcitriol modestly promoted osteoclast maturation, it strongly inhibited osteoclast lineage commitment from its progenitor monocyte by increasing Smad1 transcription via vitamin D receptor and enhancing BMP-Smad1 activation, which in turn led to increased IκBα expression and decreased NF-κB activation and NFATc1 expression, with IκBα being a Smad1 target gene...
March 31, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28369518/misregulation-of-calcium-handling-proteins-promotes-hyperactivation-of-calcineurin-nfat-signaling-in-skeletal-muscle-of-dm1-mice
#8
Aymeric Ravel-Chapuis, Guy Bélanger, Jocelyn Côté, Robin N Michel, Bernard J Jasmin
Myotonic Dystrophy type 1 (DM1) is caused by an expansion of CUG repeats in DMPK mRNAs. This mutation affects alternative splicing through misregulation of RNA-binding proteins. Amongst pre-mRNAs that are misspliced, several code for proteins involved in calcium homeostasis suggesting that calcium-handling and signaling are perturbed in DM1. Here, we analyzed expression of such proteins in DM1 mouse muscle. We found that the levels of several sarcoplasmic reticulum proteins (SERCA1, sarcolipin and calsequestrin) are altered, likely contributing to an imbalance in calcium homeostasis...
March 27, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28350111/melittin-inhibits-osteoclast-formation-through-the-downregulation-of-the-rankl-rank-signaling-pathway-and-the-inhibition-of-interleukin-1%C3%AE-in-murine-macrophages
#9
Jung-Yoon Choe, Seong-Kyu Kim
Melittin is a major toxic component of bee venom (Apis mellifera). It is not known whether melittin is involved in bone metabolism and osteoclastogenesis. The aim of this study was to determine the role of melittin in the regulation of osteoclastogenesis. In vitro osteoclastogenesis assays were performed using mouse RAW 264.7 cells and bone marrow-derived macrophages (BMMs) treated with receptor activator of nuclear factor-κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). Morphologic and functional analyses for osteoclast-like multinucleated cells (MNCs) were performed by tartrate-resistant acid phosphatase (TRAP) staining, F-actin staining and pit formation methods...
February 3, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28341745/phospholipase-c-related-but-catalytically-inactive-protein-prip-upregulates-osteoclast-differentiation-via-calcium-calcineurin-nfatc1-signaling
#10
Ayako Murakami, Miho Matsuda, Yui Harada, Masato Hirata
Phospholipase C-related, but catalytically inactive protein (PRIP) was previously identified as a novel inositol 1,4,5-trisphosphate-binding protein with a domain organization similar to that of phospholipase C-δ, but lacking phospholipase activity. We recently showed that PRIP gene knockout (KO) in mice increases bone formation and concomitantly decreases bone resorption, resulting in increased bone mineral density and trabecular bone volume. However, the role of PRIP in osteoclastogenesis has not yet been fully elucidated...
March 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28339032/clc-7-ostm1-contribute-to-the-ability-of-tea-polyphenols-to-maintain-bone-homeostasis-in-c57bl-6-mice-protecting-against-fluorosis
#11
Bing-Yun Li, Yan-Hui Gao, Jun-Rui Pei, Yan-Mei Yang, Wei Zhang, Dian-Jun Sun
Epidemiological investigations indicate that certain ingredients in tea bricks can antagonize the adverse effects of fluoride. Tea polyphenols (TPs), the most bioactive ingredient in tea bricks, have been demonstrated to be potent bone-supporting agents. ClC‑7 is known to be crucial for osteoclast (OC) bone resorption. Thus, in this study, we investigated the potential protective effects of TPs against fluorosis using a mouse model and explored the underlying mechanisms with particular focus on ClC‑7...
May 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28338087/gs%C3%AE-controls-cortical-bone-quality-by-regulating-osteoclast-differentiation-via-camp-pka-and-%C3%AE-catenin-pathways
#12
Girish Ramaswamy, Hyunsoo Kim, Deyu Zhang, Vitali Lounev, Joy Y Wu, Yongwon Choi, Frederick S Kaplan, Robert J Pignolo, Eileen M Shore
Skeletal bone formation and maintenance requires coordinate functions of several cell types, including bone forming osteoblasts and bone resorbing osteoclasts. Gsα, the stimulatory subunit of heterotrimeric G proteins, activates downstream signaling through cAMP and plays important roles in skeletal development by regulating osteoblast differentiation. Here, we demonstrate that Gsα signaling also regulates osteoclast differentiation during bone modeling and remodeling. Gnas, the gene encoding Gsα, is imprinted...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28335757/sophorae-flos-extract-inhibits-rankl-induced-osteoclast-differentiation-by-suppressing-the-nf-%C3%AE%C2%BAb-nfatc1-pathway-in-mouse-bone-marrow-cells
#13
Jeong-Mi Kim, Jung-Han Lee, Guem-San Lee, Eun-Mi Noh, Hyun-Kyung Song, Dong Ryun Gu, Seong-Cheol Kim, Seoung Hoon Lee, Kang-Beom Kwon, Young-Rae Lee
BACKGROUND: Sophorae Flos (SF) is a composite of flowers and buds of Styphnolobium japonicum (L.) Schott and has been used in traditional Korean and Chinese medicine for the treatment of hemostasis and inflammation. Previous studies reported that SF possesses anti-obesity properties, as well as anti-allergic, anti-proliferative, and anti-inflammatory activities. However, the effect of SF in bone resorption has not been studies. In this study, we examined the potential of SF extract (SFE) to inhibit receptor activator of NF-κB ligand (RANKL) -induced osteoclast differentiation in cultured mouse-derived bone marrow macrophages (BMMs)...
March 23, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28335442/in-vitro-and-in-vivo-effects-of-gracilaria-verrucosa-extracts-on-osteoclast-differentiation
#14
Kwang-Jin Kim, Yong-Jin Lee, Yun-Ho Hwang, Kyung-Yun Kang, Sung-Tae Yee, Young-Jin Son
Bone remodeling, a physiological process characterized by bone formation by osteoblasts and bone resorption by osteoclasts, is important for the maintenance of healthy bone in adult humans. Osteoclasts play a critical role in bone erosion and osteoporosis and are bone-specific multinucleated cells generated through differentiation of monocyte/macrophage lineage precursors. Receptor activator of NF-κB ligand (RANKL) has been reported to induce osteoclast differentiation. In this study, we explored whether Gracilaria verrucosa extracts (GE) could affect RANKL-mediated osteoclast differentiation...
March 14, 2017: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/28327665/akirin2-regulates-proliferation-and-differentiation-of-porcine-skeletal-muscle-satellite-cells-via-erk1-2-and-nfatc1-signaling-pathways
#15
Xiaoling Chen, Yanliu Luo, Zhiqing Huang, Gang Jia, Guangmang Liu, Hua Zhao
Akirin2, a novel nuclear factor, plays an important role in myogenesis. To investigate the role of Akirin2 in proliferation and differentiation of porcine skeletal muscle satellite cells, Akirin2 overexpression and Akirin2 silence technologies were employed. Our results showed that overexpression of Akirin2 markedly enhanced the proliferation and differentiation of porcine skeletal muscle satellite cells, whereas silencing of Akirin2 got the opposite results. Furthermore, our results showed that Akirin2 affected proliferation and differentiation of porcine skeletal muscle satellite cells through extracellular-signal regulated kinase-1/2 (ERK1/2) and NFATc1 signaling pathways...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28327458/nfatc1-expression-as-a-prognosticator-in-urothelial-carcinoma-of-the-upper-urinary-tract
#16
Takashi Kawahara, Satoshi Inoue, Kazutoshi Fujita, Taichi Mizushima, Hiroki Ide, Seiji Yamaguchi, Hiroaki Fushimi, Norio Nonomura, Hiroshi Miyamoto
We recently found that NFATc1, a member of the NFAT family and a key regulator of the immune response, could induce bladder carcinogenesis and cancer progression. In this study, we immunohistochemically stained for NFATc1 in upper urinary tract urothelial carcinoma (UUTUC) specimens and paired nonneoplastic urothelial tissues. NFATc1 was positive in 51 [52%; 40 (40%) weak (1+), 9 (9%) moderate (2+), and 2 (2%) strong (3+)] of 99 UUTUCs, which was significantly higher than in benign urothelium [30 (36%) of 83; 28 (34%) weak and 2 (2%) moderate] (0 vs 1+/2+/3+, P=...
March 16, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28317936/priming-of-transcriptional-memory-responses-via-the-chromatin-accessibility-landscape-in-t-cells
#17
Wen Juan Tu, Kristine Hardy, Christopher R Sutton, Robert McCuaig, Jasmine Li, Jenny Dunn, Abel Tan, Vedran Brezar, Melanie Morris, Gareth Denyer, Sau Kuen Lee, Stephen J Turner, Nabila Seddiki, Corey Smith, Rajiv Khanna, Sudha Rao
Memory T cells exhibit transcriptional memory and "remember" their previous pathogenic encounter to increase transcription on re-infection. However, how this transcriptional priming response is regulated is unknown. Here we performed global FAIRE-seq profiling of chromatin accessibility in a human T cell transcriptional memory model. Primary activation induced persistent accessibility changes, and secondary activation induced secondary-specific opening of previously less accessible regions associated with enhanced expression of memory-responsive genes...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28315458/cyperus-rotundus-l-extract-suppresses-rankl-induced-osteoclastogenesis-through-nfatc1-c-fos-downregulation-and-prevent-bone-loss-in-ovx-induced-osteoporosis-rat
#18
Chang-Jun Kum, Eun-Young Kim, Jae-Hyun Kim, Bina Lee, Ju-Hee Min, Jun Heo, Jong-Hyun Kim, Mijung Yeom, Youngjoo Sohn, Hyuk-Sang Jung
ETHNOPHARMACOLOGICAL RELEVANCE: Cyperus Rotundus L. (CyR) has been widely used for the treatment of gynecologic disorder. Recent studies have reported that CyR can prevent the formation of cystic follicles and ovarian malfunction. However, the effects of CyR on osteoclastogenesis and postmenopausal osteoporosis remain unknown. AIM OF THE STUDY: This study was aimed to investigate the preventive effects of CyR on RANKL-induced osteoclast formation and ovariectomy (OVX)-induced bone loss...
March 15, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28314855/def6-restrains-osteoclastogenesis-and-inflammatory-bone-resorption
#19
Nikolaus Binder, Christine Miller, Masaki Yoshida, Kazuki Inoue, Shinichi Nakano, Xiaoyu Hu, Lionel B Ivashkiv, Georg Schett, Alessandra Pernis, Steven R Goldring, F Patrick Ross, Baohong Zhao
Inflammatory bone resorption mediated by osteoclasts is a major cause of morbidity and disability in many inflammatory disorders, including rheumatoid arthritis (RA). The mechanisms that regulate osteoclastogenesis and bone resorption in inflammatory settings are complex and have not been well elucidated. In this study, we identify the immunoregulator differentially expressed in FDCP 6 homolog (Def6) as a novel inhibitor of osteoclastogenesis in physiological and inflammatory conditions. Def6 deficiency in Def6(-/-) mice enhanced the sensitivity of osteoclast precursors to the physiological osteoclastogenic inducer receptor activator for NF-κB ligand, and Def6(-/-) osteoclasts formed actin rings...
March 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28292468/microrna-34a-targets-regulator-of-calcineurin-1-to-modulate-endothelial-inflammation-after-fetal-cardiac-bypass-in-goat-placenta
#20
Hai-Yun Yuan, Cheng-Bin Zhou, Ji-Mei Chen, Xiao-Bing Liu, Shu-Sheng Wen, Gang Xu, Jian Zhuang
INTRODUCTION: Placental dysfunction characterized by vascular endothelial inflammation is one of the most notable responses to fetal cardiac bypass. Regulator of calcineurin 1 (RCAN1) is an important regulator of inflammatory responses. MicroRNAs (miRNAs) are essential post-transcriptional modulators of gene expression, and miRNA-34a (miR-34a) was showed to activate vascular endothelial inflammation. We hypothesized that miR-34a may be a key regulator of placental dysfunction after fetal cardiac bypass...
March 2017: Placenta
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