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https://www.readbyqxmd.com/read/28240358/an-advanced-tri-culture-model-to-evaluate-the-dynamic-interplay-among-osteoblasts-osteoclasts-and-endothelial-cells
#1
Stefania Pagani, Paola Torricelli, Francesca Veronesi, Francesca Salamanna, Simona Cepollaro, Milena Fini
The dynamic metabolism and the numerous roles of bone tissue necessitate a suitable in vitro model to represent them. In order to investigate the interaction among the several cell types composing bone microenvironment, we studied a tri-culture model including human osteoblasts (OBs), osteoclasts (OCs) and endothelial cells (HUVEC). While OBs are essential for bone deposition and OCs for bone resorption, the vasculature is necessary to provide growth factors, nutrients and oxygen in the mature tissue. The results of this study showed a strong mutual influence between OBs, OCs and HUVEC in term of proliferation, viability and activity (release of ALP, Coll I, OPG, RANKL, VEGF, CTSK, TGFβ and IL-6)...
February 27, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28240263/mir-21-deficiency-inhibits-osteoclast-function-and-prevents-bone-loss-in-mice
#2
Cheng-Hu Hu, Bing-Dong Sui, Fang-Ying Du, Yi Shuai, Chen-Xi Zheng, Pan Zhao, Xiao-Rui Yu, Yan Jin
MicroRNAs emerge as critical post-transcriptional regulators in bone metabolism. We have previously reported in vitro that miR-21 promotes osteogenesis, while studies have also revealed miR-21 as a regulator of osteoclastogenesis and a promoter of osteoclast differentiation in vitro. However, in vivo data are still lacking in identifying skeletal function of miR-21, particularly its effects on osteoporosis. Here, using miR-21 knockout (miR-21(-/-)) mice, we investigated effects of miR-21 on bone development, bone remodeling and bone loss...
February 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28239034/effects-of-low-intensity-pulsed-ultrasound-on-osteoclasts-analysis-with-goldfish-scales-as-a-model-of-bone
#3
Taizo Hanmoto, Yoshiaki Tabuchi, Mika Ikegame, Takashi Kondo, Kei-Ichiro Kitamura, Masato Endo, Isao Kobayashi, Hiroyuki Mishima, Toshio Sekiguchi, Makoto Urata, Azusa Seki, Sachiko Yano, Atsuhiko Hattori, Nobuo Suzuki
The effects of low-intensity pulsed ultrasound (LIPUS) on osteoclastogenesis were examined using fish scales that had both osteoclasts and osteoblasts. The binding of the receptor activator of NF-κB ligand (RANKL) in osteoblasts to the receptor activator of NF-κB (RANK) in osteoclasts induced osteoclastogenesis. Therefore, we focused on RANK/RANKL signaling. After 6 h of incubation following LIPUS treatment, mRNA expression of RANKL increased significantly. Resulting from the increased RANKL mRNA level, the expression of transcription-regulating factors significantly increased after 6 h of incubation, and then the mRNA expression of functional genes was significantly up-regulated after 12 h of incubation...
2017: Biomedical Research
https://www.readbyqxmd.com/read/28236164/evaluation-of-the-effects-of-the-combination-of-autologous-mesenchymal-stem-cells-and-platelet-rich-plasma-on-structural-bone-allograft-healing
#4
Chang-Goo Park, Min Wook Joo, Jinyoung Jeong, Yong-Koo Kang, Da-Reum Lee
In this study, we evaluated the efficacy of the combination of autologous mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) for enhancing structural allogenic bone graft healing in rabbits. For these experiments segmental bone defects (1.5-2 cm) were generated on femoral diaphysis of New Zealand white rabbits and reconstructed via structural allogenic bone grafting and additional intramedullary nail fixation. The structural allografts were subsequently wrapped with Gelfoam containing autologous MSCs and PRP, or PRP alone (control)...
February 24, 2017: Cell and Tissue Banking
https://www.readbyqxmd.com/read/28235628/denosumab-treated-giant-cell-tumor-of-bone-its-histologic-spectrum-and-potential-diagnostic-pitfalls
#5
Pablo Daniel Roitman, Federico Jauk, Germán Luis Farfalli, José Ignacio Albergo, Luis Alberto Aponte-Tinao
Giant cell tumor of bone (GCT) is a locally aggressive, rarely metastasizing primary bone neoplasm that occurs most frequently in the epiphysis of long bones of young adults. It is composed of round, oval or elongated mononuclear cells admixed with osteoclast-like giant cells that express receptor activator of nuclear factor- қB (RANK). The mononuclear stromal cells express RANK ligand (RANKL), a mediator of osteoclast activation. Denosumab, a monoclonal antibody that inhibits RANKL reducing tumor-associated bone lysis, has been used to treat selected cases of GCT...
February 21, 2017: Human Pathology
https://www.readbyqxmd.com/read/28229177/advanced-glycation-end-product-3-age3-increases-apoptosis-and-the-expression-of-sclerostin-by-stimulating-tgf-%C3%AE-expression-and-secretion-in-osteocyte-like-mlo-y4-a2-cells
#6
Masakazu Notsu, Ippei Kanazawa, Ayumu Takeno, Maki Yokomoto-Umakoshi, Ken-Ichiro Tanaka, Toru Yamaguchi, Toshitsugu Sugimoto
Advanced glycation end products (AGEs) cause bone fragility due to deterioration in bone quality. We previously reported that AGE3 induced apoptosis and inhibited differentiation via increased transforming growth factor (TGF)-β signaling in osteoblastic cells. Additionally, we demonstrated that AGE3 increased apoptosis and sclerostin expression and decreased receptor activator of nuclear factor-κB ligand (RANKL) expression in osteocyte-like cells. However, it remains unclear whether TGF-β signaling is involved in the effects of AGEs on apoptosis and the expression of sclerostin and RANKL in osteocytes...
February 22, 2017: Calcified Tissue International
https://www.readbyqxmd.com/read/28229176/denosumab-for-the-treatment-of-mastocytosis-related-osteoporosis-a-case-series
#7
Giovanni Orsolini, Irene Gavioli, Gaia Tripi, Ombretta Viapiana, Davide Gatti, Luca Idolazzi, Roberta Zanotti, Maurizio Rossini
The purpose of this study was to investigate the therapeutic effect of denosumab, an anti-RANKL monoclonal antibody for the treatment of bone loss in indolent systemic mastocytosis (ISM) patients intolerant to bisphosphonates. Four patients underwent upon informed consent a treatment with denosumab 60 mg administered subcutaneously every 6 months with the same regimen used for postmenopausal osteoporosis. Bone mineral density (BMD) was measured at lumbar and femoral sites at baseline and after 1 year. C-terminal telopeptide of collagen type I (CTX), bone alkaline phosphatase (bALP) and tryptase serum level were determined at baseline and after 12 months with fasting blood samples withdrawals...
February 22, 2017: Calcified Tissue International
https://www.readbyqxmd.com/read/28228781/denosumab-is-really-effective-in-the-treatment-of-osteoporosis-secondary-to-hypogonadism-in-prostate-carcinoma-patients-a-prospective-randomized-multicenter-international-study
#8
Carlo Doria, Paolo Tranquilli Leali, Federico Solla, Gianluca Maestretti, Massimo Balsano, Robero Mario Scarpa
INTRODUCTION: Osteoporosis is a complication of androgen deprivation therapy (ADT) in men with prostate carcinoma. The best defense against osteoporosis in prostate cancer is to identify patients with a high risk for fracture during the first clinical visit, select an effective anti-osteoporosis agent, and advise the patient to change his lifestyle and diet to prevent further bone loss. New agents include denosumab, a human monoclonal antibody that inhibits the RANK ligand (RANKL). RANKL promotes the formation, activity, and survival of osteoclasts and, thus, supports the breakdown of bone...
September 2016: Clinical Cases in Mineral and Bone Metabolism
https://www.readbyqxmd.com/read/28223547/cabozantinib-targets-bone-microenvironment-modulating-human-osteoclast-and-osteoblast-functions
#9
Marco Fioramonti, Daniele Santini, Michele Iuliani, Giulia Ribelli, Paolo Manca, Nicola Papapietro, Filippo Spiezia, Bruno Vincenzi, Vincenzo Denaro, Antonio Russo, Giuseppe Tonini, Francesco Pantano
Cabozantinib, a c-MET and vascular endothelial growth factor receptor 2 inhibitor, demonstrated to prolong progression free survival and improve skeletal disease-related endpoints in castration-resistant prostate cancer and in metastatic renal carcinoma. Our purpose is to investigate the direct effect of cabozantinib on bone microenvironment using a total human model of primary osteoclasts and osteoblasts.Osteoclasts were differentiated from monocytes isolated from healthy donors; osteoblasts were derived from human mesenchymal stem cells obtained from bone fragments of orthopedic surgery patients...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28220293/effects-of-bisphosphonates-on-osteogenesis-and-osteoclastogenesis-signaling-during-the-endochondral-ossification-of-growing-rats
#10
Eloiza Rezende, Vivian Bradaschia-Correa, Fabio Siviero, Lucas M B Ambrosio, Victor E Arana-Chavez
Osteoclasts and chondroclasts are necessary, during endochondral ossification, for the resorption of primary bone and calcified cartilage septa, respectively. The bisphosphonates inhibit mineralized tissue resorption by various mechanisms according to the different types of this drug, which can affect bone remodeling during skeletal growth. The objective of the present study is to analyze the way that alendronate (ALN) and etidronate (ETN) can affect osteoclastogenesis and bone formation during endochondral ossification of the long bones of growing rats...
February 20, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28216630/smurf2-regulates-bone-homeostasis-by-disrupting-smad3-interaction-with-vitamin-d-receptor-in-osteoblasts
#11
Zhan Xu, Matthew B Greenblatt, Guang Yan, Heng Feng, Jun Sun, Sutada Lotinun, Nicholas Brady, Roland Baron, Laurie H Glimcher, Weiguo Zou
Coordination between osteoblasts and osteoclasts is required for bone health and homeostasis. Here we show that mice deficient in SMURF2 have severe osteoporosis in vivo. This low bone mass phenotype is accompanied by a pronounced increase in osteoclast numbers, although Smurf2-deficient osteoclasts have no intrinsic alterations in activity. Smurf2-deficient osteoblasts display increased expression of RANKL, the central osteoclastogenic cytokine. Mechanistically, SMURF2 regulates RANKL expression by disrupting the interaction between SMAD3 and vitamin D receptor by altering SMAD3 ubiquitination...
February 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/28214531/the-skeletal-developmental-toxicity-of-chlormequat-chloride-and-its-underlying-mechanisms
#12
Dan Huang, Shuang Wu, Xiaohong Hou, Lixia Jia, Qinghe Meng, Hongqian Chu, Jianjun Jiang, Lanqin Shang, Weidong Hao
Chlormequat Chloride (CCC), a widely used plant growth regulator, could decrease body weight in animals; however, the mechanism has not been well studied. This study was designed to evaluate the skeletal development toxicity of CCC on pubertal male Sprague-Dawley (SD) rats and to investigate whether CCC impacts the development of chondrocyte, osteoblast and osteoclast through growth hormone (GH) and insulin like growth factor 1 (IGF-I). Rats from 23 to 70 on postnatal days were exposed to CCC daily by gavage at doses of 0, 75, 150, and 300mg/kg bw/d...
February 15, 2017: Toxicology
https://www.readbyqxmd.com/read/28213978/estrogens-and-androgens-inhibit-association-of-rankl-with-the-pre-osteoblast-membrane-through-post-translational-mechanisms
#13
Anthony Martin, Jiali Yu, Jian Xiong, Aysha B Khalid, Benita Katzenellenbogen, Sung Hoon Kim, John A Katzenellenbogen, Suchinda Malaivijitnond, Yankel Gabet, Susan A Krum, Baruch Frenkel
We have recently demonstrated that RUNX2 promoted, and 17-β-Estradiol (E2) diminished, association of RANKL with the cell membrane in pre-osteoblast cultures. Here we show that, similar to E2, dihydrotestosterone (DHT) diminishes association of RANKL and transiently transfected GFP-RANKL with the pre-osteoblast membrane without decreasing total RANKL mRNA or protein levels. Diminution of membrane-associated RANKL was accompanied with marked suppression of osteoclast differentiation from co-cultured pre-osteoclasts, even though DHT increased, not decreased, RANKL concentrations in pre-osteoblast conditioned media...
February 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28211012/f4-80-inhibits-osteoclast-differentiation-via-downregulation-of-nuclear-factor-of-activated-t-cells-cytoplasmic-1
#14
Ju-Hee Kang, Jung-Sun Sim, Ting Zheng, Mijung Yim
Osteoclastogenesis is an essential process in bone metabolism, which can be induced by RANKL stimulation. The F4/80 glycoprotein is a member of the EGF-transmembrane 7 (TM7) family and has been established as a specific cell-surface marker for murine macrophages. This study aimed to identify the role of F4/80 in osteoclastogenesis. Using mouse bone marrow-derived macrophages (BMMs), we observed that the mRNA level of F4/80 was dramatically reduced as these cells differentiated into osteoclasts. Furthermore, osteoclastogenesis was decreased in F4/80(high) BMMs compared to F4/80(-/low) BMMs...
February 16, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28209986/nf-%C3%AE%C2%BAb-signaling-regulates-cell-autonomous-regulation-of-cxcl10-in-breast-cancer-4t1-cells
#15
Won Jong Jin, Bongjun Kim, Darong Kim, Hea-Young Park Choo, Hong-Hee Kim, Hyunil Ha, Zang Hee Lee
The chemokine CXCL10 and its receptor CXCR3 play a role in breast cancer metastasis to bone and osteoclast activation. However, the mechanism of CXCL10/CXCR3-induced intracellular signaling has not been fully investigated. To evaluate CXCL10-induced cellular events in the mouse breast cancer cell line 4T1, we developed a new synthetic CXCR3 antagonist JN-2. In this study, we observed that secretion of CXCL10 in the supernatant of 4T1 cells was gradually increased during cell growth. JN-2 inhibited basal and CXCL10-induced CXCL10 expression and cell motility in 4T1 cells...
February 17, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28209487/lipoxin-a4-suppresses-osteoclastogenesis-in-raw264-7-cells-and-prevents-ovariectomy-induced-bone-loss
#16
Changyu Liu, Hanfeng Guan, Cong Cai, Feng Li, Jun Xiao
Lipoxin A4 (LXA4; 5S, 6R, 15Strihydroxy- 7,9,13-trans-11-eicosatetraenoic acid) is a metabolic product of arachidonic acid under the action of lipoxidase. This lipid molecule plays important roles in several biological functions, especially inflammatory processes. In vivo, LXA4 regulates the inflammatory response through several signaling pathways. Its mechanism suggests that it might have an effect on osteoclastogenesis and bone loss. Using both in vitro and in vivo studies, it was here observed that LXA4 could significantly inhibit the formation and function of osteoclasts and these effects could be blocked by Boc-2, the specific inhibitor of FPR2/ALX (the receptor of LXA4)...
February 13, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28208958/radiological-and-histopathological-outcome-of-giant-cell-tumor-of-femur-with-denosumab-treatment-a-case-report
#17
Preethi Dileep Menon, R Krishnakumar, Annie Jojo
Giant Cell Tumour of Bone (GCTB) is a benign but locally aggressive osteolytic skeletal neoplasm of young adults consisting of giant cells expressing RANK (Receptor Activator of Nuclear Factor-κB) and mesenchymal spindle-like stromal cells expressing RANKL (RANK ligand). The interaction of these cells leads to bone resorption. Recently, the RANKL inhibitor, denosumab, has demonstrated activity against giant-cell tumours. The current article reports a case of a Giant cell tumour of left distal femur with pathological fracture...
December 2016: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28208071/anthocyanin-suppresses-cocrmo-particle-induced-osteolysis-by-inhibiting-ikk%C3%AE-%C3%AE-mediated-nf-%C3%AE%C2%BAb-signaling-in-a-mouse-calvarial-model
#18
Yamin Li, Juehong Li, Bin Li, Hui Qin, Xiaochun Peng, Yaochao Zhao, Yunsu Chen
Wear particle-induced osteolysis and bone resorption have been identified as critical factors of implant failure and total joint revision, in which nuclear factor kappa B (NF-κB) signaling and chronic inflammation have been shown to play key roles. Although anthocyanin is known to have anti-inflammatory function via blocking NF-κB pathway, it is still unclear whether anthocyanin has a protective effect on particle-induced osteolysis. In the present study, we aimed to investigate the detailed effects and the underlying mechanism of anthocyanin on CoCrMo particle-induced osteolysis in a mouse calvavial model...
February 13, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28204822/melittin-inhibits-osteoclast-formation-through-the-downregulation-of-the-rankl-rank-signaling-pathway-and-the-inhibition-of-interleukin-1%C3%AE-in-murine-macrophages
#19
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...
March 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28203164/successful-treatment-of-advanced-primary-cutaneous-apocrine-carcinoma-on-the-scrotum-with-systemic-chemotherapy-and-radiotherapy-followed-by-denosumab
#20
Sadanori Furudate, Taku Fujimura, Akira Tsukada, Yota Sato, Takanori Hidaka, Kayo Tanita, Yumi Kambayashi, Takahiro Haga, Akira Hashimoto, Setsuya Aiba
Primary cutaneous apocrine carcinoma (PCAC) is a rare and highly aggressive cutaneous adnexal type of tumor that has a high metastasis rate and a poor prognosis. Although there are several case reports describing the successful treatment of PCAC with chemoradiotherapy or molecular targeting therapy, no standard therapy for the treatment of advanced PCAC has been established yet. Since receptor activator of nuclear factor kappa-B ligand (RANKL) is expressed in cancers of apocrine origin, leading to immunosuppression at the tumor site, we hypothesized that targeting RANKL with denosumab might be useful for the treatment of PCAC...
January 2017: Case Reports in Oncology
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