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Osteoclasts

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https://www.readbyqxmd.com/read/28102206/g%C3%AE-13-negatively-controls-osteoclastogenesis-through-inhibition-of-the-akt-gsk3%C3%AE-nfatc1-signalling-pathway
#1
Mengrui Wu, Wei Chen, Yun Lu, Guochun Zhu, Liang Hao, Yi-Ping Li
Many positive signalling pathways of osteoclastogenesis have been characterized, but negative signalling pathways are less well studied. Here we show by microarray and RNAi that guanine nucleotide-binding protein subunit α13 (Gα13) is a negative regulator of osteoclastogenesis. Osteoclast-lineage-specific Gna13 conditional knockout mice have a severe osteoporosis phenotype. Gna13-deficiency triggers a drastic increase in both osteoclast number and activity (hyper-activation), mechanistically through decreased RhoA activity and enhanced Akt/GSK3β/NFATc1 signalling...
January 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28101679/inhibitory-effect-of-saliva-on-osteoclastogenesis-in-vitro-requires-toll-like-receptor-4-signaling
#2
Heinz-Dieter Müller, Jordi Caballé-Serrano, Adrian Lussi, Reinhard Gruber
OBJECTIVES: Saliva can suppress osteoclastogenesis, but the underlying mechanism has not been discovered yet. Considering that endotoxins suppress osteoclastogenesis in bone marrow cultures and that saliva contains endotoxins, it was reasonable to hypothesize that the impact of saliva on osteoclastogenesis requires toll-like receptor 4 signaling. MATERIAL AND METHODS: To test this hypothesis, we blocked toll-like receptor 4 signaling with TAK-242 in the presence of saliva in murine bone marrow cultures...
January 18, 2017: Clinical Oral Investigations
https://www.readbyqxmd.com/read/28100862/-bone-flap-resorption-after-cranioplasty-in-pediatric-patients-report-of-2-cases
#3
Rintaro Yokoyama, Takeshi Mikami, Shouhei Noshiro, Kei Miyata, Kentaro Toyama, Katsuya Komatsu, Noriaki Kikuchi, Tadashi Hasegawa, Nobuhiro Mikuni
Aseptic bone flap resorption, a rare complication after cranioplasty following decompressive craniectomy, is more likely to develop in children. We experienced two cases of aseptic bone flap resorption and identified potential pathophysiological mechanisms through histological findings. In the first case, an 11-year-old girl underwent decompressive craniectomy due to brain swelling with contusion. An autologous bone flap was cryopreserved for four months. Twenty-five months after cranioplasty with autologous bone flap, aseptic bone flap resorption was observed, and cranioplasty was performed with ceramic bone...
January 2017: No Shinkei Geka. Neurological Surgery
https://www.readbyqxmd.com/read/28100034/murine-rankl-mesenchymal-stromal-cells-display-an-osteogenic-differentiation-defect-improved-by-a-rankl-expressing-lentiviral-vector
#4
Francesca Schena, Ciro Menale, Emanuela Caci, Lorenzo Diomede, Eleonora Palagano, Camilla Recordati, Monica Sandri, Anna Tampieri, Ileana Bortolomai, Valentina Capo, Claudia Pastorino, Arinna Bertoni, Marco Gattorno, Alberto Martini, Anna Villa, Elisabetta Traggiai, Cristina Sobacchi
Autosomal Recessive Osteopetrosis (ARO) is a severe bone disease characterized by increased bone density due to impairment in osteoclast resorptive function or differentiation. Hematopoietic stem cell transplantation (HSCT) is the only available treatment; however, this therapy is not effective in RANKL-dependent ARO, since in bone this gene is mainly expressed by cells of mesenchymal origin. Of note, whether lack of RANKL production might cause a defect also in the bone marrow (BM) stromal compartment, possibly contributing to the pathology, is unknown...
January 18, 2017: Stem Cells
https://www.readbyqxmd.com/read/28098926/relevance-of-osteoclast-specific-enzyme-activities-in-cell-based-in-vitro-resorption-assays
#5
A Bernhardt, K Koperski, M Schumacher, M Gelinsky
Cell-based in vitro resorption assays are an important tool to simulate the in vivo biodegradation of resorbable bone graft materials and to predict their clinical performance. The present study analyses the activity of osteoclast-specific enzymes as potential surrogate measures for classical pit assay, which is not applicable on irregular structured materials. Osteoclasts derived from human peripheral blood mononuclear cells were cultivated on different surfaces: calcium phosphate bone cements (CPC), dentin discs, osteoblast-derived extracellular matrix (ECM) and tissue culture polystyrene as control...
January 18, 2017: European Cells & Materials
https://www.readbyqxmd.com/read/28098793/osteocyte-alterations-induce-osteoclastogenesis-in-an-in-vitro-model-of-gaucher-disease
#6
Constanza Bondar, Maximiliano Ormazabal, Andrea Crivaro, Malena Ferreyra-Compagnucci, María Victoria Delpino, Paula Adriana Rozenfeld, Juan Marcos Mucci
Gaucher disease (GD) is caused by mutations in the glucosylceramidase β (GBA 1) gene that confer a deficient level of activity of glucocerebrosidase (GCase). This deficiency leads to the accumulation of the glycolipid glucocerebroside in the lysosomes of cells, mainly in the monocyte/macrophage lineage. Its mildest form is Type I GD, characterized by non-neuronopathic involvement. Bone compromise is the most disabling aspect of the Gaucher disease. However, the pathophysiological aspects of skeletal alterations are not yet fully understood...
January 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28097375/hypoxia-induced-fibroblast-growth-factor-11-stimulates-osteoclast-mediated-resorption-of-bone
#7
Helen J Knowles
Over-activation of osteoclasts is directly responsible for pathological bone loss in conditions such as rheumatoid arthritis and cancer metastasis to bone. Hypoxia is a common feature of these conditions, associated with poor prognosis, which also stimulates osteoclast-mediated bone resorption via induction of the hypoxia-inducible transcription factor HIF-1α. Here, we investigate the effects of fibroblast growth factor 11 (FGF11) on osteoclast function. FGF11 is an intracellular FGF that was induced both by hypoxia (2% O2, p < 0...
January 18, 2017: Calcified Tissue International
https://www.readbyqxmd.com/read/28096061/connexin37-deficiency-alters-organic-bone-matrix-cortical-bone-geometry-and-increases-wnt-%C3%AE-catenin-signaling
#8
Rafael Pacheco-Costa, Jay R Kadakia, Emily G Atkinson, Joseph M Wallace, Lilian I Plotkin, Rejane D Reginato
Deletion of connexin (Cx) 37 in mice leads to increased cancellous bone mass due to defective osteoclast differentiation. Paradoxically; however, Cx37-deficient mice exhibit reduced cortical thickness accompanied by higher bone strength, suggesting a contribution of Cx37 to bone matrix composition. Thus, we investigated whether global deletion of Cx37 alters the composition of organic bone extracellular matrix. Five-month-old Cx37(-/-) mice exhibited increased marrow cavity area, and periosteal and endocortical bone surface resulting in higher total area in tibia compared to Cx37(+/+) control mice...
January 13, 2017: Bone
https://www.readbyqxmd.com/read/28095295/hematopoietic-stem-cell-transplantation-corrects-osteopetrosis-in-a-child-carrying-a-novel-homozygous-mutation-in-the-fermt3-gene
#9
Eleonora Palagano, Mary A Slatter, Paolo Uva, Ciro Menale, Anna Villa, Mario Abinun, Cristina Sobacchi
Osteopetrosis (OPT) is a rare skeletal disorder with phenotypic and genotypic heterogeneity: a variety of clinical features besides the bony defect may be present, and at least ten different genes are known to be involved in the disease pathogenesis. In the framework of this heterogeneity, we report the clinical description of a neonate, first child of consanguineous parents, who had osteoclast-rich osteopetrosis and bone marrow failure in early life, but no other usual classical features of infantile malignant OPT, such as visual or hearing impairments...
January 14, 2017: Bone
https://www.readbyqxmd.com/read/28095260/differential-expression-and-roles-of-secreted-frizzled-related-protein-5-and-the-wingless-homolog-wnt5a-in-periodontitis
#10
T Maekawa, P Kulwattanaporn, K Hosur, H Domon, M Oda, Y Terao, T Maeda, G Hajishengallis
The Wingless/integrase-1 (Wnt) family of protein ligands and their functional antagonists, secreted frizzled-related proteins (sFRPs), regulate various biological processes ranging from embryonic development to immunity and inflammation. Wnt5a and sFRP5 comprise a typical ligand/antagonist pair, and the former molecule was recently detected at the messenger RNA (mRNA) level in human periodontitis. The main objective of this study was to investigate the interrelationship of expression of Wnt5a and sFRP5 in human periodontitis (as compared to health) and to determine their roles in inflammation and bone loss in an animal model...
January 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28094562/effects-of-bisphosphonate-administration-on-cleft-bone-graft-in-a-rat-model
#11
Nicole Cheng, Juyoung Park, Jeffrey Olson, Taewoo Kwon, Deborah Lee, Rachel Lim, Sandy Ha, Reuben Kim, Xinli Zhang, Kang Ting, Sotirios Tetradis, Christine Hong
OBJECTIVE:   Bone grafts in patients with cleft lip and palate can undergo a significant amount of resorption. The aim of this study was to investigate the effects of bisphosphonates (BPs) on the success of bone grafts in rats. DESIGN:   Thirty-five female 15-week-old Fischer F344 Inbred rats were divided into the following experimental groups, each receiving bone grafts to repair an intraoral CSD: (1) Graft/saline: systemic administration of saline and (2) systemic administration of zoledronic acid immediately following surgery (graft/BP/T0), (3) 1 week postoperatively (graft/BP/T1), and (4) 3 weeks postoperatively (graft/BP/T2)...
January 17, 2017: Cleft Palate-craniofacial Journal
https://www.readbyqxmd.com/read/28094240/ectopic-bone-formation-by-gel-derived-bioactive-glass-poly-l-lactide-co-glycolide-composites-in-a-rabbit-muscle-model
#12
Joanna Filipowska, Katarzyna Cholewa-Kowalska, Jarosław Wieczorek, Danuta Semik, Zbigniew Dąbrowski, Maria Łączka, Anna M Osyczka
In this study we aimed to assess the in vivo osteoinductive properties of two composite scaffolds made of PLGA (poly-L-lactide-co-glycolide) and two types of gel-derived bioactive glasses, namely a high silica S2 bioactive glass (S2-PLGA composites) or high lime A2 bioactive glass (A2-PLGA composites). To achieve that, the potential of the composites to induce ectopic bone formation in a rabbit muscle has been examined along with the control PLGA scaffold. Cylinder-like scaffolds of 7  ×  3 mm (width  ×  height) were implanted into pouches created in the latissimus dorsi muscle of 18 New Zealand rabbits...
January 17, 2017: Biomedical Materials
https://www.readbyqxmd.com/read/28094214/primary-intraosseous-adenoid-cystic-carcinoma-of-the-mandible-a-comprehensive-review-and-analysis-of-four-new-cases-with-emphasis-on-morphologic-immunophenotypic-and-molecular-characteristics
#13
Jing Han, Ting Gu, Xi Yang, Longwei Hu, Ronghui Xia, Zhen Tian, Jiang Li, Ling Zhu, Liqun Xu, Chunye Zhang
OBJECTIVE: To comprehensively review the clinical manifestations, imaging, diagnosis, treatment, and pathologic features of primary intraosseous adenoid cystic carcinoma (PIACC) of the mandible and analyze PIACC histopathology and molecular features in four cases. STUDY DESIGN: We reviewed the literature and retrospectively studied four cases of PIACC. RESULTS: The clinical and imaging findings of PIACC are similar to other malignant or borderline-malignant mandible tumors...
November 11, 2016: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
https://www.readbyqxmd.com/read/28093892/multinucleated-giant-cells-in-the-implant-bed-of-bone-substitutes-are-foreign-body-giant-cells-new-insights-into-the-material-mediated-healing-process
#14
Mike Barbeck, Patrick Booms, Ronald Unger, Verena Hoffmann, Robert Sader, Charles James Kirkpatrick, Shahram Ghanaati
In addition to macrophages, multinucleated giant cells (MNGCs) are involved in the tissue reaction to a variety of biomaterials. Especially in the case of bone substitute materials it has been assumed that the MNGCs are osteoclasts, based on the chemical and physical similarity of many materials to the calcified matrix and the bony environment in which they are used. However, many studies indicate that these cells belong to the cell line of the foreign body giant cells (FBGCs), which are of "inflammatory origin", although they have been shown to possess both a pro- and also anti-inflammatory phenotype...
January 17, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28093526/cathepsin-k-deficiency-ameliorates-systemic-lupus-erythematosus-like-manifestations-in-faslpr-mice
#15
Yi Zhou, Huimei Chen, Li Liu, Xueqing Yu, Galina K Sukhova, Min Yang, Vasileios C Kyttaris, Isaac E Stillman, Bruce Gelb, Peter Libby, George C Tsokos, Guo-Ping Shi
Cysteinyl cathepsin K (CatK) is expressed in osteoclasts to mediate bone resorption, but is also inducible under inflammatory conditions. Fas(lpr) mice on a C57BL/6 background develop spontaneous systemic lupus erythematosus-like manifestations. Although normal mouse kidneys expressed negligible CatK, those from Fas(lpr) mice showed elevated CatK expression in the glomeruli and tubulointerstitial space. Fas(lpr) mice also showed elevated serum CatK levels. CatK deficiency in Fas(lpr) mice reduced all tested kidney pathologies, including glomerulus and tubulointerstitial scores, glomerulus complement C3 and IgG deposition, chemokine expression and macrophage infiltration, and serum autoantibodies...
January 16, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28092987/emerging-treatment-approaches-for-myeloma-related-bone-disease
#16
Maria Gavriatopoulou, Meletios A Dimopoulos, Efstathios Kastritis, Evangelos Terpos
Multiple myeloma is characterized by the presence of osteolytic lesions that leads to devastating skeletal-related events in the majority of patients. Myeloma bone disease is attributed to increased osteoclastic and suppressed osteoblastic activity. Areas covered: Bisphosphonates remain the main treatment option, however they have limitations on their own. Understanding the pathogenesis of myeloma bone disease may provide a roadmap for new therapeutic approaches. The pathway of RANKRANKLOPG pathway has revealed denosumab, a monoclonal antibody targeting RANKL as a novel emerging therapy for myeloma-related bone disease...
January 17, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28091516/osteopontin-regulates-macrophage-activation-and-osteoclast-formation-in-hypertensive-patients-with-vascular-calcification
#17
Qian Ge, Cheng-Chao Ruan, Yu Ma, Xiao-Feng Tang, Qi-Hong Wu, Ji-Guang Wang, Ding-Liang Zhu, Ping-Jin Gao
Vascular calcification (VC) is a highly regulated ectopic mineral deposition process involving immune cell infiltration in the vasculatures, which has been recognized to be promoted by hypertension. The matricellular glycoprotein osteopontin (OPN) is strongly induced in myeloid cells as a potential inflammatory mediator of vascular injury. This study aims to examine whether OPN is involved in the regulation of macrophage activation and osteoclast formation in hypertensive subjects with VC. We firstly found an increased proportion of CD11c+CD163- pro-inflammatory peripheral monocytes in hypertensive subjects with VC compared to those without VC by flow cytometric analysis...
January 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28089586/natural-uranium-impairs-the-differentiation-and-the-resorbing-function-of-osteoclasts
#18
Tatiana Gritsaenko, Valérie Pierrefite-Carle, Thomas Lorivel, Véronique Breuil, Georges F Carle, Sabine Santucci-Darmanin
BACKGROUND: Uranium is a naturally occurring radionuclide ubiquitously present in the environment. The skeleton is the main site of uranium long-term accumulation. While it has been shown that natural uranium is able to perturb bone metabolism through its chemical toxicity, its impact on bone resorption by osteoclasts has been poorly explored. Here, we examined for the first time in vitro effects of natural uranium on osteoclasts. METHODS: The effects of uranium on the RAW 264...
January 9, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28088671/melatonin-attenuates-titanium-particle-induced-osteolysis-via-activation-of-wnt-%C3%AE-catenin-signaling-pathway
#19
Zichuan Ping, Xuanyang Hu, Liangliang Wang, Jiawei Shi, Yunxia Tao, Xiexing Wu, Zhenyang Hou, Xiaobin Guo, Wen Zhang, Huilin Yang, Yaozeng Xu, Zhirong Wang, Dechun Geng
: Wear debris-induced inhibition of bone regeneration and extensive bone resorption were common features in peri-prosthetic osteolysis (PPO). Here, we investigated the effect of melatonin on titanium particle-stimulated osteolysis in a murine calvariae model and mouse-mesenchymal-stem cells (mMSCs) culture system. Melatonin inhibited titanium particle-induced osteolysis and increased bone formation at osteolytic sites, confirmed by radiological and histomorphometric data. Furthermore, osteoclast numbers decreased dramatically in the low- and high-melatonin administration mice, as respectively, compared with the untreated animals...
January 11, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28087412/pain-prediction-by-serum-biomarkers-of-bone-turnover-in-people-with-knee-osteoarthritis-an-observational-study-of-tracp5b-and-cathepsin-k-in-oa
#20
Lilian N Nwosu, Maximilian Allen, Laura Wyatt, Janet L Huebner, Victoria Chapman, David A Walsh, Virginia B Kraus
OBJECTIVES: To investigate serum biomarkers, tartrate resistant acid phosphatase 5b (TRAcP5b) and cathepsin K, indicative of osteoclastic bone resorption, and their relationship to pain and pain change in knee osteoarthritis (OA). METHODS: Sera and clinical data were collected from 129 people (97 with 3-year follow-up) with knee OA from the Prediction of Osteoarthritis Progression (POP) cohort. Knee OA-related outcomes in POP included: WOMAC pain, NHANES I (pain, aching and stiffness), subchondral sclerosis, and radiographically determined tibiofemoral and patellofemoral OA...
January 10, 2017: Osteoarthritis and Cartilage
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