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Osteoclastogenesis

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https://www.readbyqxmd.com/read/28723554/hypoxia-sensitive-commd1-integrates-signaling-and-cellular-metabolism-in-human-macrophages-and-suppresses-osteoclastogenesis
#1
Koichi Murata, Celestia Fang, Chikashi Terao, Eugenia G Giannopoulou, Ye Ji Lee, Min Joon Lee, Se-Hwan Mun, Seyeon Bae, Yu Qiao, Ruoxi Yuan, Moritoshi Furu, Hiromu Ito, Koichiro Ohmura, Shuichi Matsuda, Tsuneyo Mimori, Fumihiko Matsuda, Kyung-Hyun Park-Min, Lionel B Ivashkiv
Hypoxia augments inflammatory responses and osteoclastogenesis by incompletely understood mechanisms. We identified COMMD1 as a cell-intrinsic negative regulator of osteoclastogenesis that is suppressed by hypoxia. In human macrophages, COMMD1 restrained induction of NF-κB signaling and a transcription factor E2F1-dependent metabolic pathway by the cytokine RANKL. Downregulation of COMMD1 protein expression by hypoxia augmented RANKL-induced expression of inflammatory and E2F1 target genes and downstream osteoclastogenesis...
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28720797/commensal-gut-microbiota-immunomodulatory-actions-in-bone-marrow-and-liver-have-catabolic-effects-on-skeletal-homeostasis-in-health
#2
Chad M Novince, Carolyn R Whittow, Johannes D Aartun, Jessica D Hathaway, Nicole Poulides, Michael B Chavez, Heidi M Steinkamp, Kaeleigh A Kirkwood, Emily Huang, Caroline Westwater, Keith L Kirkwood
Despite knowledge the gut microbiota regulates bone mass, mechanisms governing the normal gut microbiota's osteoimmunomodulatory effects on skeletal remodeling and homeostasis are unclear in the healthy adult skeleton. Young adult specific-pathogen-free and germ-free mice were used to delineate the commensal microbiota's immunoregulatory effects on osteoblastogenesis, osteoclastogenesis, marrow T-cell hematopoiesis, and extra-skeletal endocrine organ function. We report the commensal microbiota has anti-anabolic effects suppressing osteoblastogenesis and pro-catabolic effects enhancing osteoclastogenesis, which drive bone loss in health...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28715463/potassium-citrate-prevents-increased-osteoclastogenesis-resulting-from-acidic-conditions-implication-for-the-treatment-of-postmenopausal-bone-loss
#3
Donatella Granchi, Elena Torreggiani, Annamaria Massa, Renata Caudarella, Gemma Di Pompo, Nicola Baldini
The extracellular acidic milieu in bones results in activation of osteoclasts (OC) and inhibition of osteoblasts (OB) causing a net loss of calcium from the skeleton and the deterioration of bone microarchitecture. Alkalinization through supplementation with potassium citrate (K citrate) has been proposed to limit the osteopenia progression, even though its pharmacological activity in bone microenvironment is not well defined. We evaluated if K citrate was able to prevent the adverse effects that acidic milieu induces on bone cells...
2017: PloS One
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
#4
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/28712894/antimicrobial-and-immunomodulatory-activity-of-host-defense-peptides-clavanins-and-ll-37-in-vitro-an-endodontic-perspective
#5
Stella Maris F Lima, Mirna S Freire, Ana Luisa O Gomes, Ana Paula C Cantuária, Flávia Rodrigues P Dutra, Beatriz S Magalhães, Maurício Gonçalves C Sousa, Ludovico Migliolo, Jeeser A Almeida, Octávio L Franco, Taia Maria B Rezende
Endodontic treatment is mainly based on root canal disinfection and its failure may be motivated by microbial resistance. Endodontic therapy can be benefitted by host defense peptides (HDPs), which are multifunctional molecules that act against persistent infection and inflammation. This study aimed to evaluate the antimicrobial, cytotoxic and immunomodulatory activity of several HDPs, namely clavanin A, clavanin A modified (MO) and LL-37, compared to intracanal medication Ca(OH)2. HDPs and Ca(OH)2 were evaluated by: (1) antimicrobial assays against Candida albicans and Enterococcus faecalis, (2) cytotoxicity assays and (3) cytokine tumor necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1, interleukin (IL)- 1α, IL-6, IL-10 and IL-12 and nitric oxide (NO) production by RAW 264...
July 13, 2017: Peptides
https://www.readbyqxmd.com/read/28711819/differentiation-potential-of-synoviocytes-derived-from-joints-with-cranial-cruciate-ligament-rupture-and-medial-patella-luxation-in-dogs
#6
H M Suranji Wijekoon, Kazuhide Toyota, Sangho Kim, Jing Fang, Eugene C Bwalya, Kenji Hosoya, Masahiro Okumura
The objective of this study was to assess the differentiation capability of synoviocytes derived from dogs with inflammatory joint conditions. Cranial cruciate ligament ruptured (CCLr) (n=12) and medial patella luxated (MPL) (n=10) knee joints of the dogs were used to collect the synovial membrane (SM). Synoviocytes were enzymatically released from the SM and analyzed by flow cytometry for specific cellular markers (CD44 and CD90) of mesenchymal stem cells (MSCs), while doing histopathology from another part of SM sections...
July 9, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28710354/ssu72-attenuates-autoimmune-arthritis-via-targeting-of-stat3-signaling-and-th17-activation
#7
Seung Hoon Lee, Eun-Kyung Kim, Jeong-Eun Kwon, Jin-Kwan Lee, DoHyeong Lee, Se-Young Kim, Hyeon-Beom Seo, Hyun Sik Na, KyoungAh Jung, Seung-Ki Kwok, Chang-Woo Lee, Sung-Hwan Park, Mi-La Cho
Signal transducer and activator of transcription 3 (STAT3) orchestrates the differentiation of several cell types, including interleukin-17 (IL-17)-releasing Th17 cells. Dysregulation of Th17 cells results in chronic inflammatory responses. Ssu72 is a C-terminal domain phosphatase required for transcriptional regulation. However, the mechanism by which Ssu72 affects STAT3 activation and Th17 cell differentiation is unclear. Here, we found that Ssu72 overexpression suppresses STAT3 activation and Th17 cell responses in vitro...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28709835/the-antimicrobial-peptide-human-%C3%AE-defensin-1-potentiates-in-vitro-osteoclastogenesis-via-activation-of-the-p44-42-mitogen-activated-protein-kinases
#8
Anupong Makeudom, Chayarop Supanchart, Pattanin Montreekachon, Sakornrat Khongkhunthian, Thanapat Sastraruji, Julaporn Krisanaprakornkit, Suttichai Krisanaprakornkit
Previous studies have demonstrated increased expression and raised levels of human β-defensin (hBD)-1 in gingival tissue and crevicular fluid of patients with chronic periodontitis and peri-implantitis, oral bone-resorbing diseases caused by enhanced osteoclastogenesis. Therefore, we aimed to investigate the effect of hBD-1 on osteoclast formation and function and to elucidate the involved signaling pathway in vitro. Human peripheral blood mononuclear cells (PBMCs) were first incubated with various doses of hBD-1 and cell viability was assayed by MTT...
July 11, 2017: Peptides
https://www.readbyqxmd.com/read/28708884/a-jak1-2-inhibitor-baricitinib-inhibits-osteoclastogenesis-by-suppressing-rankl-expression-in-osteoblasts-in-vitro
#9
Kohei Murakami, Yasuhiro Kobayashi, Shunsuke Uehara, Takako Suzuki, Masanori Koide, Teruhito Yamashita, Midori Nakamura, Naoyuki Takahashi, Hiroyuki Kato, Nobuyuki Udagawa, Yukio Nakamura
The Janus kinases (Jaks) are hubs in the signaling process of more than 50 cytokine or hormone receptors. However, the function of Jak in bone metabolism remains to be elucidated. Here, we showed that the inhibition of Jak1 and/or Jak2 in osteoblast-lineage cells led to impaired osteoclastogenesis due to the reduced expression of receptor activator of nuclear factor-κB ligand (RANKL). Murine calvaria-derived osteoblasts induced differentiation of bone marrow cells into osteoclasts in the presence of 1,25-dihydroxyvitamin D3 (1,25D3) and prostaglandin E2 (PGE2) in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28708287/regulation-of-rankl-induced-osteoclastogenesis-by-ring-finger-protein-rnf114
#10
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/28705683/periodontal-ligament-fibroblasts-as-a-cell-model-to-study-osteogenesis-and-osteoclastogenesis-in-fibrodysplasia-ossificans-progressiva
#11
Teun J de Vries, Ton Schoenmaker, Dimitra Micha, Jolanda Hogervorst, Siham Bouskla, Tim Forouzanfar, Gerard Pals, Coen Netelenbos, E Marelise W Eekhoff, Nathalie Bravenboer
Fibrodysplasia Ossificans Progressiva (FOP) is a progressive disease characterized by periods of heterotopic ossification of soft connective tissues, including ligaments. Though progress has been made in recent years in unraveling the underlying mechanism, patient-derived cell models are necessary to test potential treatment options. Periodontal ligament fibroblasts (PLF) from extracted teeth can be used to study deviant bone modeling processes in vitro since these cells are derived from genuine ligaments. They further provide a tool to study the hitherto unknown role of the bone morphogenesis protein receptor type 1 (BMPR-1) Activin A type 1 receptor ACVR1-R206H mutation in osteoclastogenesis...
July 10, 2017: Bone
https://www.readbyqxmd.com/read/28698612/eif2%C3%AE-signaling-regulates-ischemic-osteonecrosis-through-endoplasmic-reticulum-stress
#12
Daquan Liu, Yunlong Zhang, Xinle Li, Jie Li, Shuang Yang, Xiaoxue Xing, Guanwei Fan, Hiroki Yokota, Ping Zhang
Osteonecrosis of the femoral head (ONFH) primarily results from ischemia/hypoxia to the femoral head, and one of the cellular manifestations is the endoplasmic reticulum (ER) stress. To understand possible linkage of ischemic osteonecrosis to the ER stress, a surgery-induced animal model was employed and salubrinal was administered to evaluate the role of ER stress. Salubrinal is a synthetic chemical that inhibits de-phosphorylation of eIF2α, and it can suppress cell death from the ER stress at a proper dose...
July 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28698171/natural-compounds-for-the-treatment-of-psoriatic-arthritis-a-proposal-based-on-multi-targeted-osteoclastic-regulation-and-on-a-preclinical-study
#13
Shiqiang Deng, Jianwen Cheng, Jinmin Zhao, Felix Yao, Jiake Xu
BACKGROUND: Psoriatic arthritis (PsA) is a chronic inflammatory arthritis affecting approximately 2% to 3% of the population globally, and is characterized by both peripheral articular manifestations and axial skeletal involvement. Conventional therapies for PsA have not been fully satisfactory, though natural products (NPs) have been shown to be highly effective and represent important treatment options for psoriasis. PsA is a multigenic autoimmune disease with both environmental and genetic factors contributing to its pathogenesis...
July 11, 2017: JMIR Research Protocols
https://www.readbyqxmd.com/read/28696515/tbhq-suppresses-osteoclastic-resorption-in-xenogeneic-treated-dentin-matrix-based-scaffolds
#14
Jingjing Sun, Jie Li, Hui Li, Hefeng Yang, Jinlong Chen, Bo Yang, Fangjun Huo, Weihua Guo, Weidong Tian
Extracellularmatrix (ECM)-based scaffolds are important for their potential therapeutic application. Treated dentin matrix (TDM), a kind of ECM, seeded with allogeneic dental follicle stem cells (TDM/aDFC) provides a suitable inductive microenvironment for tooth root regeneration. Considering the limited sources, xenogeneic TDM (xTDM) is a possible alternative to allogeneic TDM; however, xTDM-based scaffold presents severe osteolysis and resorption lacunae causing regenerated tooth root failure. Immune response-induced excessive osteoclastogenesis plays a critical role in xenogeneic scaffold osteolysis and resorption...
July 11, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28692257/targeting-osteocytes-to-attenuate-early-breast-cancer-bone-metastasis-by-theranostic-upconversion-nanoparticles-with-responsive-plumbagin-release
#15
Han Qiao, Zhaowen Cui, Shengbing Yang, Dingkun Ji, Yugang Wang, Ying Yang, Xiuguo Han, Qiming Fan, An Qin, Tingyu Wang, Xiao-Peng He, Wenbo Bu, Tingting Tang
The early detection and thus treatment of breast cancer bone metastasis remain a big challenge clinically. As the most abundant cells within bone tissue, osteocytes have been found to manipulate the activity of early cancer bone metastasis by its crosstalk with cancer cells and osteoclasts. However, conventional bone-targeting nanomedicine has limited bone-lesion specificity and ignores the vital role of osteocytes during breast cancer bone metastasis. Also, it lacks detailed insight into the therapeutic mechanisms, which hinders the following translational practice...
July 13, 2017: ACS Nano
https://www.readbyqxmd.com/read/28687489/fas-s1p1-crosstalk-via-nf-%C3%AE%C2%BAb-activation-in-osteoclasts-controls-subchondral-bone-remodeling-in-murine-tmj-arthritis
#16
Islamy Rahma Hutami, Takashi Izawa, Akiko Mino-Oka, Takehiro Shinohara, Hiroki Mori, Akihiko Iwasa, Eiji Tanaka
Enhanced turnover of subchondral trabecular bone is a hallmark of rheumatoid arthritis (RA) and it results from an imbalance between bone resorption and bone formation activities. To investigate the formation and activation of osteoclasts which mediate bone resorption, a Fas-deficient MRL/lpr mouse model which spontaneously develops autoimmune arthritis and exhibits decreased bone mass was studied. Various assays were performed on subchondral trabecular bone of the temporomandibular joint (TMJ) from MRL/lpr mice and MRL+/+ mice...
July 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28682648/kinase-inhibitors-of-the-igf-1r-as-a-potential-therapeutic-agent-for-rheumatoid-arthritis
#17
Hiroshi Tsushima, Shinji Morimoto, Maki Fujishiro, Yuko Yoshida, Kunihiro Hayakawa, Takuya Hirai, Tomoko Miyashita, Keigo Ikeda, Ken Yamaji, Kenji Takamori, Yoshinari Takasaki, Iwao Sekigawa, Naoto Tamura
We have previously shown that the inhibition of connective tissue growth factor (CTGF) is a potential therapeutic strategy against rheumatoid arthritis (RA). CTGF consists of four distinct modules, including the insulin-like growth factor binding protein (IGFBP). In serum, insulin-like growth factors (IGFs) bind IGFBPs, interact with the IGF-1 receptor (IGF-1 R), and regulate anabolic effects and bone metabolism. We investigated the correlation between IGF-1 and the pathogenesis of RA, and the inhibitory effect on osteoclastogenesis and angiogenesis of the small molecular weight kinase inhibitor of the IGF-1 R, NVP-AEW541, against pathogenesis of RA in vitro...
July 6, 2017: Autoimmunity
https://www.readbyqxmd.com/read/28681916/luteoloside-prevents-lipopolysaccharide-induced-osteolysis-and-suppresses-rankl-induced-osteoclastogenesis-through-attenuating-rankl-signaling-cascades
#18
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
#19
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
#20
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
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