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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/28442323/the-ace-2-ang1-7-mas-cascade-enhances-bone-structure-and-metabolism-following-angiotensin-ii-type-1-receptor-blockade
#2
Hatem M Abuohashish, Mohammed M Ahmed, Dina Sabry, Mahmoud M Khattab, Salim S Al-Rejaie
The renin angiotensin system (RAS) regulates numerous systemic functions and is expressed locally in skeletal tissues. Angiotensin1-7 (Ang1-7) is a beneficial member of the RAS, and the therapeutic effects of a large number of angiotensin receptors blockers (ARBs) are mediated by an Ang1-7-dependent cascade. This study examines whether the reported osteo-preservative effects of losartan are mediated through the angiotensin converting enzyme2 (ACE-2)/Ang1-7/Mas pathway in ovariectomized (OVX) rats. Sham and OVX animals received losartan (10mg/kg/d p...
April 22, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28438834/rankl-cytokine-enhances-tnf-induced-osteoclastogenesis-independently-of-tnf-receptor-associated-factor-traf-6-by-degrading-traf3-in-osteoclast-precursors
#3
Zhenqiang Yao, Wei Lei, Rong Duan, Yanyun Li, Lu Luo, Brendan F Boyce
Cytokines, including receptor activator of nuclear factor kappa B ligand (RANKL) and TNF, induce increased osteoclast (OC) formation and bone loss in postmenopausal osteoporosis and inflammatory arthritides. RANKL and TNF can independently induce OC formation in vitro from WT OC precursors via TNF receptor-associated factor (TRAF) adaptor proteins, which bind to their receptors. Of these, only TRAF6 is required for RANKL-induced osteoclastogenesis in vitro. However, the molecular mechanisms involved remain incompletely understood...
April 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28438779/human-alternative-macrophages-populate-calcified-areas-of-atherosclerotic-lesions-and-display-impaired-rankl-induced-osteoclastic-bone-resorption-activity
#4
Giulia Chinetti-Gbaguidi, Mehdi Daoudi, Mickael Rosa, Manjula Vinod, Loïc Louvet, Corinne Copin, Melanie Fanchon, Jonathan Vanhoutte, Bruno Derudas, Loic Belloy, Stephan Haulon, Christophe Zawadzki, Sophie Susen, Ziad A Massy, Jérôme Eeckhoute, Bart Staels
Rationale: Vascular calcification is a process similar to bone formation leading to an inappropriate deposition of calcium phosphate minerals in advanced atherosclerotic plaques. Monocyte-derived macrophages, located in atherosclerotic lesions and presenting heterogeneous phenotypes, from classical pro-inflammatory M1 to alternative anti-inflammatory M2 macrophages, could potentially display osteoclast-like functions. Objective: To characterize the phenotype of macrophages located in areas surrounding the calcium deposits in human atherosclerotic plaques...
April 24, 2017: Circulation Research
https://www.readbyqxmd.com/read/28437887/influence-of-sinomenine-upon-mesenchymal-stem-cells-in-osteoclastogenesis
#5
Biao Zhou, Xiaolong Lu, Zhi Tang, Dan Liu, Youliang Zhou, Peng Zeng, Hui Xiong
With the advent of aging, the morbidity rates of such diseases as osteoarthritis, rheumatoid arthritis, and osteoporosis has witnessed a significant increase. As a common rattan drug, sinomenine (SIN) has been widely applied for the treatment of various arthritic diseases in traditional Chinese medicine (TCM) clinics. Given that SIN has been reported to inhibit the expression of Prostaglandin E2 (PGE2) in several types of cells, in this study, the influence of SIN treatment on PGE2 expression in mesenchymal stem cells (MSCs), thereby changing the osteoprotegerin (OPG) receptor/activator for the nuclear factor-κ B ligand (RANKL) ratio, was investigated...
April 19, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28436956/identification-of-subepithelial-mesenchymal-cells-that-induce-iga-and-diversify-gut-microbiota
#6
Kazuki Nagashima, Shinichiro Sawa, Takeshi Nitta, Masanori Tsutsumi, Tadashi Okamura, Josef M Penninger, Tomoki Nakashima, Hiroshi Takayanagi
Immunoglobulin A (IgA) maintains a symbiotic equilibrium with intestinal microbes. IgA induction in the gut-associated lymphoid tissues (GALTs) is dependent on microbial sampling and cellular interaction in the subepithelial dome (SED). However it is unclear how IgA induction is predominantly initiated in the SED. Here we show that previously unrecognized mesenchymal cells in the SED of GALTs regulate bacteria-specific IgA production and diversify the gut microbiota. Mesenchymal cells expressing the cytokine RANKL directly interact with the gut epithelium to control CCL20 expression and microfold (M) cell differentiation...
April 24, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28431214/interferon-%C3%AE-released-by-activated-cd8-t-lymphocytes-impairs-the-calcium-resorption-potential-of-osteoclasts-in-calcified-human-aortic-valves
#7
Edit Nagy, Yang Lei, Eduardo Martínez-Martínez, Simon C Body, Florian Schlotter, Michael Creager, Alexander Assmann, Kamal Khabbaz, Peter Libby, Göran K Hansson, Elena Aikawa
Calcium content in patients with calcific aortic valve disease (CAVD) correlates with the severity of stenosis. In CAVD, activated T lymphocytes localize with osteoclast regions; however, the functional consequences of this association remain unknown. We hypothesized that CD8(+) T cells modulate calcification in CAVD. Explanted CAVD valves (n = 52) dissected into noncalcified and calcified portions were subjected to mRNA extraction, real-time quantitative PCR, enzyme-linked immunosorbent assay, and immunohistochemical analyses...
April 18, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28429052/the-skeletal-impact-of-the-chemotherapeutic-agent-etoposide
#8
A J Koh, B P Sinder, P Entezami, L Nilsson, L K McCauley
Effects of the chemotherapeutic agent etoposide on the skeleton were determined in mice. Numbers of bone marrow cells were reduced and myeloid cells were increased. Bone volume was significantly decreased with signs of inhibition of bone formation. Etoposide after pre-treatment with zoledronic acid still reduced bone but overall bone volume was higher than with etoposide alone. INTRODUCTION: Chemotherapeutics target rapidly dividing tumor cells yet also impact hematopoietic and immune cells in an off target manner...
April 20, 2017: Osteoporosis International
https://www.readbyqxmd.com/read/28427810/synthesis-of-novel-5-6-dehydrokawain-analogs-as-osteogenic-inducers-and-their-action-mechanisms
#9
Momochika Kumagai, Keisuke Nishikawa, Takashi Mishima, Izumi Yoshida, Masahiro Ide, Keiko Koizumi, Munetomo Nakamura, Yoshiki Morimoto
An imbalance between bone resorption by osteoclasts and bone formation by osteoblasts can cause bone loss and bone-related disease. In a previous search for natural products that increase osteogenic activity, we found that 5,6-dehydrokawain (1) from Alpinia zerumbet promotes osteoblastogenesis. In this study, we synthesized and evaluated series of 5,6-dehydrokawain analogs. Our structure-activity relationships revealed that alkylation of para or meta position of aromatic ring of 1 promote osteogenic activity...
April 6, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28426652/cheminformatics-aided-discovery-of-small-molecule-protein-protein-interaction-ppi-dual-inhibitors-of-tumor-necrosis-factor-tnf-and-receptor-activator-of-nf-%C3%AE%C2%BAb-ligand-rankl
#10
Georgia Melagraki, Evangelos Ntougkos, Vagelis Rinotas, Christos Papaneophytou, Georgios Leonis, Thomas Mavromoustakos, George Kontopidis, Eleni Douni, Antreas Afantitis, George Kollias
We present an in silico drug discovery pipeline developed and applied for the identification and virtual screening of small-molecule Protein-Protein Interaction (PPI) compounds that act as dual inhibitors of TNF and RANKL through the trimerization interface. The cheminformatics part of the pipeline was developed by combining structure-based with ligand-based modeling using the largest available set of known TNF inhibitors in the literature (2481 small molecules). To facilitate virtual screening, the consensus predictive model was made freely available at: http://enalos...
April 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28425620/periarticular-bone-loss-in-arthritis-is-induced-by-autoantibodies-against-citrullinated-vimentin
#11
Cecilia Engdahl, Holger Bang, Katharina Dietel, Stefanie C Lang, Ulrike Harre, Georg Schett
Periarticular bone loss is a long known but yet insufficiently understood phenomenon in patients with rheumatoid arthritis. This study investigated whether autoimmunity against citrullinated proteins is causally involved in triggering periarticular bone loss. Periarticular bone loss was studied in the standard antigen induced arthritis (AIA) mouse model with methylated bovine serum albumin (mBSA) as well as modified model with mutated citrullinated vimentin (MCV) alone or in combination with mBSA. Periarticular bone loss, subchondral osteoclastogenesis as well as local expression of cytokines, osteoclast genes and PAD enzymes were assessed after arthritis induction...
April 20, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28425564/osteoblast-role-in-osteoarthritis-pathogenesis
#12
REVIEW
Nicola Maruotti, Addolorata Corrado, Francesco Paolo Cantatore
Even if osteoarthritis pathogenesis is still poorly understood, numerous evidences suggest that osteoblasts dysregulation plays a key role in osteoarthritis pathogenesis. An abnormal expression of OPG and RANKL has been described in osteoarthritis osteoblasts, which is responsible for abnormal bone remodeling and decreased mineralization. Alterations in genes expression are involved in dysregulation of osteoblast function, bone remodeling and mineralization, leading to osteoarthritis development. Moreover, osteoblasts produce numerous transcription factors, growth factors and other proteic molecules which are involved in osteoarthritis pathogenesis...
April 20, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28421466/parathyroid-diseases-and-t-cells
#13
REVIEW
M Neale Weitzmann, Roberto Pacifici
PURPOSE OF REVIEW: This review summarizes studies into the permissive role of T cells in the bone catabolic effects of hyperparathyroidism and parathyroid hormone (PTH). RECENT FINDINGS: Work in animals combined with recent translational studies in humans now highlight the potent amplificatory action of T cells on PTH-induced bone resorption. Mechanistic animal studies reveal a complex pathway by which PTH exploits natural self-renewal functions of CD4(+) T cells, to drive TNFα production that promotes formation of IL-17A secreting Th17 T cells...
April 18, 2017: Current Osteoporosis Reports
https://www.readbyqxmd.com/read/28419987/extracellular-matrix-mediates-bmp-2-in-a-model-of-temporomandibular-joint-osteoarthritis
#14
Maya Shirakura, Vardit Kram, Jennifer Robinson, Sheena Sikka, Tina M Kilts, Sunil Wadhwa, Marian F Young
Temporomandibular joint (TMJ) osteoarthritis (OA) is a complex disease that affects both cartilage and subchondral bone. It is accompanied by loss of extracellular matrix (ECM) and may be controlled by bone morphogenetic protein-2 (BMP-2). We analyzed the effect of BMP-2 in both cartilage and subchondral bone in a TMJ-OA animal model that is deficient in biglycan (Bgn) and fibromodulin (Fmod) (Bgn-/-Fmod-/-). Whole mandibles were dissected from 3-week-old wild-type (WT) and Bgn-/-Fmod-/- mice and incubated with and without 250 µg/mL BMP-2 for 2 days using an explant culture system...
April 19, 2017: Cells, Tissues, Organs
https://www.readbyqxmd.com/read/28419519/deletion-of-a-distal-rankl-gene-enhancer-delays-progression-of-atherosclerotic-plaque-calcification-in-hypercholesterolemic-mice
#15
Sohel Shamsuzzaman, Melda Onal, Hillary C St John, J Wesley Pike
Receptor activator of NF-κB ligand (RANKL) is a TNFα-like cytokine which mediates diverse physiological functions including bone remodeling and immune regulation. RANKL has been identified in atherosclerotic lesions; however, its role in atherosclerotic plaque development remains elusive. An enhancer located 75kb upstream of the murine RANKL gene's transcription start site designated D5 is important for its calciotropic hormone- and cytokine-mediated expression. Here, we determined the impact of RANKL levels in atherosclerotic plaque development in the D5 enhancer-null (D5(-/-) ) mice in an atherogenic Apoe(-/-) background fed a high-fat diet (HFD)...
April 17, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28417335/poor-prognosis-of-patients-with-triple-negative-breast-cancer-can-be-stratified-by-rank-and-rankl-dual-expression
#16
Monica E Reyes, Takeo Fujii, Daniel Branstetter, Savitri Krishnamurthy, Hiroko Masuda, Xiaoping Wang, James M Reuben, Wendy A Woodward, Beatrice J Edwards, Gabriel N Hortobagyi, Debu Tripathy, William C Dougall, Bedrich L Eckhardt, Naoto T Ueno
PURPOSE: As clinical studies have correlated RANK expression levels with survival in breast cancer, and that RANK signaling is dependent on its cognate ligand RANKL, we hypothesized that dual protein expression further stratifies the poor outcome in TNBC. METHODS: RANK mRNA and protein expression was evaluated in TNBC using genomic databases, cell lines and in a tissue microarray of curated primary tumor samples derived from 87 patients with TNBC. RANK expression was evaluated either by Mann-Whitney U test on log-normalized gene expression data or by Student's t test on FACS data...
April 17, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28416991/can-denosumab-be-a-substitute-competitor-or-complement-to-bisphosphonates
#17
REVIEW
Su Young Kim, Hwoe Gyeong Ok, Christof Birkenmaier, Kyung Hoon Kim
Osteoblasts, originating from mesenchymal cells, make the receptor activator of the nuclear factor kappa B ligand (RANKL) and osteoprotegerin (OPG) in order to control differentiation of activated osteoclasts, originating from hematopoietic stem cells. When the RANKL binds to the RANK of the pre-osteoclasts or mature osteoclasts, bone resorption increases. On the contrary, when OPG binds to the RANK, bone resorption decreases. Denosumab (AMG 162), like OPG (a decoy receptor), binds to the RANKL, and reduces binding between the RANK and the RANKL resulting in inhibition of osteoclastogenesis and reduction of bone resorption...
April 2017: Korean Journal of Pain
https://www.readbyqxmd.com/read/28414988/response-of-mandibular-condyles-of-juvenile-and-adult-rats-to-abnormal-occlusion-and-subsequent-exemption
#18
Guang Zeng, Bin Kuang, Wen-Xing Xun, Gao-Tong Ren, Ke-Wen Wei
OBJECTIVE: The adaptation capacities of the mandibular condyle in response to mechanical stimuli might be different between juveniles and adults, but has not been compared. This study aimed to investigate whether abnormal molar occlusion and subsequent molar extraction could lead to different remodeling responses in the mandibular condyles of juvenile and adult rats. METHODS: Abnormal molar occlusion (AMO) was established in the 5- and 16-wk old rats by moving their maxillary left and mandibular right third molars distally...
March 28, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/28414795/negative-feedback-loop-of-bone-resorption-by-nfatc1-dependent-induction-of-cadm1
#19
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/28414140/shear-stress-inhibits-il-17a-mediated-induction-of-osteoclastogenesis-via-osteocyte-pathways
#20
Chongshan Liao, Tianfan Cheng, Shuai Wang, Chengfei Zhang, Lijian Jin, Yanqi Yang
Interleukin (IL)-17 is crucial to osteoclast differentiation and activation. Osteocytes support osteoclast formation and are thought to orchestrate bone remodeling in response to fluid flow. The contribution of IL-17 to osteocyte-related bone resorption remains unclear. Here, we used the osteocyte-like MLO-Y4 cell line to examine the role of IL-17 and fluid flow in osteoclastogenesis. It was the first time to demonstrate that IL-17A promoted MLO-Y4 cell proliferation, enhanced expression of receptor activator of nuclear factor κ-B ligand (RANKL) and tumor necrosis factor-α (TNF-α), and induced osteoclastogenesis when MLO-Y4 cells were co-cultured with bone marrow-derived macrophage (BMM) cells...
April 14, 2017: Bone
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