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Osteoclastogenesis

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https://www.readbyqxmd.com/read/28637206/improving-combination-osteoporosis-therapy-in-a-preclinical-model-of-heightened-osteoanabolism
#1
Yu Shao, Selene Hernandez-Buquer, Paul Childress, Keith R Stayrook, Marta B Alvarez, Hannah Davis, Lilian Plotkin, Yongzheng He, Keith W Condon, David B Burr, Stuart J Warden, Alexander G Robling, Feng-Chun Yang, Ronald C Wek, Matthew R Allen, Joseph P Bidwell
Combining anti-catabolic agents with parathyroid hormone (PTH) to enhance bone mass has yielded mixed results in osteoporosis patients. Towards the goal of enhancing the efficacy of these regimens, we tested their utility in combination with loss of the transcription factor Nmp4 since disabling this gene amplifies PTH-induced increases in trabecular bone in mice by boosting osteoblast secretory activity. We addressed whether combining a sustained anabolic response with an anti-catabolic results in superior bone acquisition compared to PTH mono-therapy...
June 20, 2017: Endocrinology
https://www.readbyqxmd.com/read/28637021/dectin-1-signaling-inhibits-osteoclastogenesis-via-il-33-induced-inhibition-of-nfatc1
#2
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/28628032/osteocyte-specific-wnt1-regulates-osteoblast-function-during-bone-homeostasis
#3
Kyu Sang Joeng, Yi-Chien Lee, Joohyun Lim, Yuqing Chen, Ming-Ming Jiang, Elda Munivez, Catherine Ambrose, Brendan H Lee
Mutations in WNT1 cause osteogenesis imperfecta (OI) and early-onset osteoporosis, identifying it as a key Wnt ligand in human bone homeostasis. However, how and where WNT1 acts in bone are unclear. To address this mechanism, we generated late-osteoblast-specific and osteocyte-specific WNT1 loss- and gain-of-function mouse models. Deletion of Wnt1 in osteocytes resulted in low bone mass with spontaneous fractures similar to that observed in OI patients. Conversely, Wnt1 overexpression from osteocytes stimulated bone formation by increasing osteoblast number and activity, which was due in part to activation of mTORC1 signaling...
June 19, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28627025/novel-rankl-de-loop-mutants-antagonize-rank-mediated-osteoclastogenesis
#4
Yizhou Wang, Aart H G van Assen, Carlos R Reis, Rita Setroikromo, Ronald van Merkerk, Ykelien L Boersma, Robbert H Cool, Wim J Quax
Bone is a dynamic tissue that is maintained by continuous renewal. An imbalance in bone resorption and bone formation can lead to a range of disorders, such as osteoporosis. The Receptor Activator of NF-κB (RANK)-RANK ligand (RANKL) pathway plays a major role in bone remodeling. Here, we investigated the effect of mutations at position I248 in the DE-loop of murine RANKL on the interaction of RANKL with RANK, and subsequent activation of osteoclastogenesis. Two single mutants, RANKL I248Y and I248K, were found to maintain binding and have the ability to reduce wild type RANKL-induced osteoclastogenesis...
June 19, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28624869/incorporation-of-cerium-oxide-into-hydroxyapatite-coating-protects-bone-marrow-stromal-cells-against-h2o2-induced-inhibition-of-osteogenic-differentiation
#5
Kai Li, Qingyi Shen, Youtao Xie, Mingyu You, Liping Huang, Xuebin Zheng
Oxidative stress exerts a key influence in osteoporosis in part by inhibiting osteogenic differentiation of bone marrow stromal cells (BMSCs). With their unique antioxidant properties and reported biocompatibility, cerium oxide (CeO2) ceramics exhibit promising potential for the treatment of osteoporosis resulting from oxidative stress. In this study, protective effects of CeO2-incorporated hydroxyapatite coatings (HA-10Ce and HA-30Ce) on the viability and osteogenic differentiation of H2O2-treated BMSCs were examined...
June 17, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/28620304/pu-erh-tea-extract-ameliorates-ovariectomy-induced-osteoporosis-in-rats-and-suppresses-osteoclastogenesis-in-vitro
#6
Titi Liu, Shihua Ding, Dan Yin, Xiangdan Cuan, Chuanqi Xie, Huanhuan Xu, Xuanjun Wang, Jun Sheng
Background and Objective: Tea drinking is associated with positive effects on bone health and may protect against osteoporosis, especially in elderly women. Pu-erh tea has many beneficial effects on human health; however, whether Pu-erh tea has anti-osteoporotic potential remains unclear. Thus, we investigated the effects of Pu-erh tea extract (PTE) on ovariectomy-induced osteoporosis in rats and on osteoclastogenesis in vitro. Methods: Female Wistar rats were divided into six groups: the sham, model, and Xian-Ling-Gu-Bao capsule (XLGB) groups, and the low-, medium-, and high-dose PTE groups...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28618255/osteocyte-regulation-of-receptor-activator-of-nf-%C3%AE%C2%BAb-ligand-osteoprotegerin-in-a-sheep-model-of-osteoporosis
#7
Thaqif El Khassawna, Felix Merboth, Deeksha Malhan, Wolfgang Böcker, Diaa E S Daghma, Sabine Stoetzel, Stefanie Kern, Fathi Hassan, Dirk Rosenbaum, Judith Langenstein, Natali Bauer, Anja Schlagenhauf, Angela Rösen-Wolff, Felix Schulze, Markus Rupp, Dirk Hose, Anja Secklinger, Anita Ignatius, Hans-Joachim Wilke, Katrin S Lips, Christian Heiss
Osteoporosis induction in a sheep model by steroid administration combined with ovariectomy recapitulates decreased bone formation and substandard matrix mineralization in patients. Recently, the role of osteocytes has been frequently addressed, with focus on their role in osteoclastogenesis. However, the quantification of receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) signaling in osteocytes was not studied in sheep. The current study reproduced the sheep model of osteoporosis to study the RANKL/OPG ratio correlation to the method of osteoporosis induction...
June 12, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28614388/osteoblast-specific-overexpression-of-complement-receptor-c5ar1-impairs-fracture-healing
#8
Stephanie Bergdolt, Anna Kovtun, Yvonne Hägele, Astrid Liedert, Thorsten Schinke, Michael Amling, Markus Huber-Lang, Anita Ignatius
The anaphylatoxin receptor C5aR1 plays an important role not only in innate immune responses, but also in bone metabolism and fracture healing, being highly expressed on immune and bone cells, including osteoblasts and osteoclasts. C5aR1 induces osteoblast migration, cytokine generation and osteoclastogenesis, however, the exact role of C5aR1-mediated signaling in osteoblasts is not entirely known. Therefore, we hypothesized that osteoblasts are essential target cells for C5a and that fracture healing should be disturbed in mice with an osteoblast-specific C5aR1 overexpression (Col1a1-C5aR1)...
2017: PloS One
https://www.readbyqxmd.com/read/28611683/pathways-that-regulate-ros-scavenging-enzymes-and-their-role-in-defense-against-tissue-destruction-in-periodontitis
#9
REVIEW
Hiroyuki Kanzaki, Satoshi Wada, Tsuyoshi Narimiya, Yuuki Yamaguchi, Yuta Katsumata, Kanako Itohiya, Sari Fukaya, Yutaka Miyamoto, Yoshiki Nakamura
Periodontitis, an inflammatory disease that affects the tissues surrounding the teeth, is a common disease worldwide. It is caused by a dysregulation of the host inflammatory response to bacterial infection, which leads to soft and hard tissue destruction. In particular, it is the excessive inflammation in response to bacterial plaque that leads to the release of reactive oxygen species (ROS) from neutrophils, which, then play a critical role in the destruction of periodontal tissue. Generally, ROS produced from immune cells exhibit an anti-bacterial effect and play a role in host defense and immune regulation...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28602725/il15ra-is-required-for-osteoblast-function-and-bone-mineralization
#10
Emanuele Loro, Girish Ramaswamy, Abhishek Chandra, Wei-Ju Tseng, Manoj K Mishra, Eileen M Shore, Tejvir S Khurana
Interleukin-15 receptor alpha (IL15RA) is an important component of interleukin-15 (IL15) pro-inflammatory signaling. In addition, IL15 and IL15RA are present in the circulation and are detected in a variety of tissues where they influence physiological functions such as muscle contractility and overall metabolism. In the skeletal system, IL15RA was previously shown to be important for osteoclastogenesis. Little is known, however, about its role in osteoblast function and bone mineralization. In this study, we evaluated bone structural and mechanical properties of an Il15ra whole-body knockout mouse (Il15ra(-/-)) and used in vitro and bioinformatic analyses to understand the role IL15/IL15RA signaling on osteoblast function...
June 5, 2017: Bone
https://www.readbyqxmd.com/read/28600846/ectopic-implantation-of-juvenile-osteochondral-tissues-recapitulates-endochondral-ossification
#11
Johnathan Ng, Yiyong Wei, Bin Zhou, Sarindr Bhumiratana, Aonnicha Burapachaisri, Edward Guo, Gordana Vunjak-Novakovic
Subcutaneous implantation in a mouse can be used to investigate tissue maturation in vivo. Here, we demonstrate that this simple model can recapitulate endochondral ossification associated with native skeletal development. By histological and μCT analysis, we investigated morphological changes of immature bovine osteochondral tissues over the course of subcutaneous implantation in immunocompromised mice for up to 10 weeks. We observed multiple similarities between the ectopic process and native endochondral ossification: (i) permanent cartilage retention in the upper zones, (ii) progressive loss of transient cartilage accompanied by bone formation at the interface, and (iii) remodeling of nascent endochondral bone into mature cancellous bone...
June 10, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28600504/amphiregulin-contained-in-nsclc-exosomes-induces-osteoclast-differentiation-through-the-activation-of-egfr-pathway
#12
Simona Taverna, Marzia Pucci, Marco Giallombardo, Maria Antonietta Di Bella, Mariacarmela Santarpia, Pablo Reclusa, Ignacio Gil-Bazo, Christian Rolfo, Riccardo Alessandro
Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths worldwide. The majority of patients are diagnosed in advanced disease stage. Bone metastasis is the most frequent complication in NSCLC resulting in osteolytic lesions. The perfect balance between bone-resorbing osteoclasts and bone-forming osteoblasts activity is lost in bone metastasis, inducing osteoclastogenesis. In NSCLC, the epidermal growth factor receptor (EGFR) pathway is constitutively activated. EGFR binds Amphiregulin (AREG) that is overexpressed in several cancers such as colon, breast and lung...
June 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28600151/splenomegaly-myeloid-lineage-expansion-and-increased-osteoclastogenesis-in-osteogenesis-imperfecta-murine
#13
Brya G Matthews, Emilie Roeder, Xi Wang, Hector Leonardo Aguila, Sun-Kyeong Lee, Danka Grcevic, Ivo Kalajzic
Osteogenesis imperfecta (OI) is a disease caused by defects in type I collagen production that results in brittle bones. While the pathology is mainly caused by defects in the osteoblast lineage, there is also elevated bone resorption by osteoclasts resulting in high bone turnover in severe forms of the disease. Osteoclasts originate from hematopoietic myeloid cells, however changes in hematopoiesis have not been previously documented in OI. In this study, we evaluated hematopoietic lineage distribution and osteoclast progenitor cell frequency in bone marrow, spleen and peripheral blood of osteogenesis imperfecta murine (OIM) mice, a model of severe OI...
June 7, 2017: Bone
https://www.readbyqxmd.com/read/28591574/mtor-inhibition-subdues-milk-disorder-caused-by-maternal-vldlr-loss
#14
HoangDinh Huynh, Wei Wei, Yihong Wan
It is unknown whether and how very-low density lipoprotein receptors (VLDLRs) impact skeletal homeostasis. Here, we report that maternal and offspring VLDLRs play opposite roles in osteoclastogenesis and bone resorption. VLDLR deletion in the offspring augments osteoclast differentiation by enhancing RANKL signaling, leading to osteoporosis. In contrast, VLDLR deletion in the mother alters milk metabolism, which inhibits osteoclast differentiation and causes osteopetrosis in the offspring. The maternal effects are dominant...
June 6, 2017: Cell Reports
https://www.readbyqxmd.com/read/28590061/porphyromonas-gingivalis-lipopolysaccharide-regulates-ephrin-eph-signalling-in-human-periodontal-ligament-fibroblasts
#15
M Li, C Zhang, L Jin, K Matsuo, Y Yang
OBJECTIVE: EphrinA2-EphA2 and ephrinB2-EphB4 critically engage in bidirectional signalling to modulate alveolar bone remodelling. The present study aimed to investigate the effects of lipopolysaccharides (LPS) derived from Porphyromonas gingivalis on ephrin/Eph signalling in periodontal ligament fibroblasts (PDLFs). MATERIAL AND METHODS: The primary cultured PDLFs were incubated in the absence (as a control) or presence of P. gingivalisLPS at 0.001-10 μg/mL for 24 hours...
June 7, 2017: Journal of Periodontal Research
https://www.readbyqxmd.com/read/28589137/microrna-16-5p-inhibits-osteoclastogenesis-in-giant-cell-tumor-of-bone
#16
Shang Sang, Zhichang Zhang, Shu Qin, Changwei Li, Yang Dong
Giant cell tumor (GCT) of bone is an aggressive skeletal tumor characterized by localized bone resorption. MicroRNA-16-5p (miR-16-5p) has been reported to be downregulated in lesions of patients with GCT, but little is known about its role in GCT. To explore the underlying function of miR-16-5p in GCT, we first detected its expression in patients with GCT. The results showed that osteoclast formation increased, whereas miR-16-5p expression considerably decreased with the severity of bone destruction. Furthermore, we found that miR-16-5p expression considerably decreased with the progression of receptor activator of nuclear factor-κB ligand- (RANKL-) induced osteoclastogenesis...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28589079/role-of-light-in-the-pathogenesis-of-joint-destruction-in-rheumatoid-arthritis
#17
Afsie Sabokbar, Sara Afrough, David J Mahoney, Yoshinobu Uchihara, Catherine Swales, Nicholas A Athanasou
AIM: To characterise the role of substitutes for receptor-activator nuclear factor kappa-B ligand (RANKL) in rheumatoid arthritis (RA) joint destruction. METHODS: Synovial fluid (SF) macrophages isolated from the knee joint of RA patients were incubated with 25 ng/mL macrophage-colony stimulating factor (M-CSF) and 50 ng/mL LIGHT (lymphotoxin-like, exhibits inducible expression and competes with herpes simplex virus glycoprotein D for herpes virus entry mediator, a receptor expressed by T lymphocytes) in the presence and absence of 25 ng/mL RANKL and 100 ng/mL osteoprotegerin (OPG) on glass coverslips and dentine slices...
May 20, 2017: World Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28587628/osteoclast-profile-of-medication-related-osteonecrosis-of-the-jaw-secondary-to-bisphosphonate-therapy-a-comparison-with-osteoradionecrosis-and-osteomyelitis
#18
Christian Gross, Manuel Weber, Kay Creutzburg, Patrick Möbius, Raimund Preidl, Kerstin Amann, Falk Wehrhan
BACKGROUND: The medication-related osteonecrosis of the jaw secondary to bisphosphonate therapy [MRONJ (BP)] is characterized by non-healing exposed bone in the maxillofacial region. The pathogenesis of MRONJ (BP) is not fully understood. Giant, hypernucleated, inactive osteoclasts were found in MRONJ (BP) tissues, which indicated that accelerated cell-cell fusion might play a role. Dendritic cell-specific transmembrane protein (DC-STAMP) is associated with the cell-cell fusion of osteoclasts and precursor cells...
June 6, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28587149/suppression-of-osteoclastogenesis-by-melatonin-a-melatonin-receptor-independent-action
#19
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
#20
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
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