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https://www.readbyqxmd.com/read/28550626/combination-breast-cancer-chemotherapy-with-doxorubicin-and-cyclophosphamide-damages-bone-and-bone-marrow-in-a-female-rat-model
#1
Chiaming Fan, Kristen R Georgiou, Howard A Morris, Ross A McKinnon, Dorothy M K Keefe, Peter R Howe, Cory J Xian
PURPOSE: Anthracyclines (including doxorubicin) are still the backbone of commonly used breast cancer chemotherapy regimens. Despite increasing use of doxorubicin and cyclophosphamide (AC) combinations for treating breast cancer, their potential to cause adverse skeletal effects remains unclear. METHODS: This study examined the effects of treatments with the AC regimen on bone and bone marrow in adult female rats. RESULTS: AC treatment for four cycles (weekly intravenous injection of 2 mg/kg doxorubicin and 20 mg/kg cyclophosphamide) resulted in a reduced volume of trabecular bone at the metaphysis, which was associated with reduced serum levels of 25-hydroxy vitamin D3 and alkaline phosphatase...
May 26, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28548288/hypermineralization-and-high-osteocyte-lacunar-density-in-osteogenesis-imperfecta-type-v-bone-indicate-exuberant-primary-bone-formation
#2
Stéphane Blouin, Nadja Fratzl-Zelman, Francis H Glorieux, Paul Roschger, Klaus Klaushofer, Joan C Marini, Frank Rauch
In contrast to "classical" forms of Osteogenesis imperfecta (OI) types I to IV, caused by a mutation in COL1A1/A2, OI type V is due to a gain-of-function mutation in the IFITM5 gene, encoding the interferon-induced transmembrane protein 5, or bone-restricted ifitm-like protein (BRIL). Its phenotype distinctly differs from OI types I to IV by absence of blue sclerae and dentinogenesis imperfecta, by the occurrence of ossification disorders like hyperplastic callus and forearm interosseous membrane ossification...
May 26, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28547661/targeting-sclerostin-in-postmenopausal-osteoporosis-focus-on-romosozumab-and-blosozumab
#3
Ian R Reid
Most current treatments for osteoporosis inhibit bone resorption and reduce total fracture numbers by about one-quarter. The identification of the osteocytic protein sclerostin as a potent regulator of bone turnover and bone density has led to the development of a new therapeutic class-agents that inhibit sclerostin activity, resulting in increased bone formation and reduced bone resorption. Romosozumab and blosozumab are monoclonal antibodies that bind to sclerostin, reducing its inhibition of Wnt signaling...
May 25, 2017: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
https://www.readbyqxmd.com/read/28543818/bone-formation-is-coupled-to-resorption-via-suppression-of-sclerostin-expression-by-osteoclasts
#4
Masanori Koide, Yasuhiro Kobayashi, Teruhito Yamashita, Shunsuke Uehara, Midori Nakamura, B Yukihiro Hiraoka, Yuki Ozaki, Tadahiro Iimura, Hisataka Yasuda, Naoyuki Takahashi, Nobuyuki Udagawa
Bone formation is coupled to bone resorption throughout life. However, it is not fully elucidated the coupling mechanisms. Using Tnfrsf11b-deficient (OPG(-/-) ) mice, in which bone formation is clearly coupled to bone resorption, we found here that osteoclasts suppress the expression of sclerostin, a Wnt antagonist, thereby promoting bone formation. Wnt/beta-catenin signals were higher in OPG(-/-) and RANKL-transgenic mice with a low level of sclerostin. Conditioned medium from osteoclast cultures (Ocl-CM) suppressed sclerostin expression in UMR106 cells and osteocyte cultures...
May 24, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28539096/influence-of-olive-oil-on-alveolar-bone-response-during-orthodontic-retention-period-rabbit-model-study
#5
Afrah K Al-Hamdany, Ali R Al-Khatib, Hafidh I Al-Sadi
OBJECTIVES: This study attempted to evaluate clinically and histologically the effects of olive oil (Ol) consumption on orthodontic relapse after the retention period. DESIGN: Thirty apparently healthy female albino rabbits, weight more than 1000 g each was used in this study. The animals were grouped randomly into six groups of five animals each: two control and four experimental groups. In control groups, the relapse was estimated either at zero day, or at the end of the fourth week after orthodontic retention period...
May 24, 2017: Acta Odontologica Scandinavica
https://www.readbyqxmd.com/read/28531813/immunomodulatory-function-of-whole-human-umbilical-cord-derived-mesenchymal-stem-cells
#6
Hao Zhang, Yanling Tao, Haihui Liu, Saisai Ren, Bin Zhang, Hu Chen
Bone marrow derived mesenchymal stem cells (MSCs) play a critical role in immune modulation. However, immunomodulatory function of whole human umbilical cord derived mesenchymal stem cells (UC-MSCs) remains unclear. In this study, UC-MSCs were separated from whole umbilical cord using a single enzyme digestion. UC-MSCs (CD73(+), CD90(+), CD105(+), and CD34(-), CD45(-), HLA-DR(-)) were differentiated into adipocytes, osteocytes and chondrocytes in vitro under specific stimulatory environments. UC-MSCs suppressed umbilical cord blood lymphocyte proliferation stimulated by mitogen, and ELISA showed that the secretion of INF-γ was downregulated, and the secretion of IL-4 was upregulated, with CD8(+) T cells markedly decreased and CD4(+) T cells changed lightly...
May 19, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28529724/recent-advances-in-the-management-of-osteoporosis
#7
REVIEW
Seiji Fukumoto, Toshio Matsumoto
There has been substantial progress in the management of patients with osteoporosis and the prevention of osteoporotic fractures. Currently available strong anti-resorptive agents are bisphosphonates and an anti-receptor activator of nuclear factor-kappa B ligand (RANKL) antibody, denosumab. Although bisphosphonates and denosumab both inhibit bone resorption and prevent vertebral and non-vertebral fractures, their mechanisms of action are different. Whereas bisphosphonates' effects on bone mineral density and fracture peak around 3 to 5 years and become plateaued, those of denosumab are maintained for up to 10 years...
2017: F1000Research
https://www.readbyqxmd.com/read/28529307/genetic-deletion-of-sost-or-pharmacological-inhibition-of-sclerostin-prevent-multiple-myeloma-induced-bone-disease-without-affecting-tumor-growth
#8
J Delgado-Calle, J Anderson, M D Cregor, K W Condon, S A Kuhstoss, L I Plotkin, T Bellido, G D Roodman
Multiple myeloma (MM) causes lytic bone lesions due to increased bone resorption and concomitant marked suppression of bone formation. Sclerostin (Scl) levels, an osteocyte-derived inhibitor of Wnt/β-catenin signaling, are elevated in MM patient sera and are increased in osteocytes in MM-bearing mice. We show here that genetic deletion of Sost, the gene encoding Scl, prevented MM-induced bone disease in an immune-deficient mouse model of early MM, and that administration of anti-Scl antibody (Scl-Ab) increased bone mass and decreases osteolysis in immune-competent mice with established MM...
May 22, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28529022/effect-of-microgravity-on-the-mesenchymal-stem-cell-characteristics-of-limbal-fibroblasts
#9
Shu-I Pao, Ke-Hung Chien, Hsin-Ting Lin, Ming-Cheng Tai, Jiann-Torng Chen, Chang-Min Liang
BACKGROUND: Mesenchymal stem cells (MSCs) are important for regenerative medicine. Limbal fibroblasts (LFs), present in the corneal limbus, have been shown to possess MSC characteristics, and can differentiate into other cell types. The current study sought to investigate the effect of microgravity on the proliferation and differentiation of LFs, and identify culture conditions to obtain a high proportion of LFs possessing MSC characteristics. METHODS: A rotary cell culture system was used to generate microgravity...
May 18, 2017: Journal of the Chinese Medical Association: JCMA
https://www.readbyqxmd.com/read/28527581/nuclear-receptors-in-skeletal-homeostasis
#10
Hao Zuo, Yihong Wan
Nuclear receptors are a family of transcription factors that can be activated by lipophilic ligands. They are fundamental regulators of development, reproduction, and energy metabolism. In bone, nuclear receptors enable bone cells, including osteoblasts, osteoclasts, and osteocytes, to sense their dynamic microenvironment and maintain normal bone development and remodeling. Our views of the molecular mechanisms in this process have advanced greatly in the past decade. Drugs targeting nuclear receptors are widely used in the clinic for treating patients with bone disorders such as osteoporosis by modulating bone formation and resorption rates...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28523374/capturing-microscopic-features-of-bone-remodeling-into-a-macroscopic-model-based-on-biological-rationales-of-bone-adaptation
#11
Young Kwan Kim, Yoshitaka Kameo, Sakae Tanaka, Taiji Adachi
To understand Wolff's law, bone adaptation by remodeling at the cellular and tissue levels has been discussed extensively through experimental and simulation studies. For the clinical application of a bone remodeling simulation, it is significant to establish a macroscopic model that incorporates clarified microscopic mechanisms. In this study, we proposed novel macroscopic models based on the microscopic mechanism of osteocytic mechanosensing, in which the flow of fluid in the lacuno-canalicular porosity generated by fluid pressure gradients plays an important role, and theoretically evaluated the proposed models, taking biological rationales of bone adaptation into account...
May 18, 2017: Biomechanics and Modeling in Mechanobiology
https://www.readbyqxmd.com/read/28523251/bone-marker-gene-expression-in-calvarial-bones-different-bone-microenvironments
#12
Osama Al-Amer
BACKGROUND: In calvarial mice, mesenchymal stem cells (MSCs) differentiate into osteoprogenitor cells and then differentiate into osteoblasts that differentiate into osteocytes, which become embedded within the bone matrix. In this case, the cells participating in bone formation include MSCs, osteoprogenitor cells, osteoblasts and osteocytes. The calvariae of C57BL/KaLwRijHsD mice consist of the following five bones: two frontal bones, two parietal bones and one interparietal bone. This study aimed to analyse some bone marker genes and bone related genes to determine whether these calvarial bones have different bone microenvironments...
December 2017: Journal of Biological Research
https://www.readbyqxmd.com/read/28515094/inhibiting-the-osteocyte-specific-protein-sclerostin-increases-bone-mass-and-fracture-resistance-in-multiple-myeloma
#13
Michelle M McDonald, Michaela R Reagan, Scott E Youlten, Sindhu T Mohanty, Anja Seckinger, Rachael L Terry, Jessica A Pettitt, Marija K Simic, Tegan L Cheng, Alyson Morse, Lawrence M T Le, David Abi-Hanna, Ina Kramer, Carolyne Falank, Heather Fairfield, Irene M Ghobrial, Paul A Baldock, David G Little, Michaela Kneissel, Karin Vanderkerken, J H Duncan Bassett, Graham R Williams, Babatunde O Oyajobi, Dirk Hose, Tri G Phan, Peter I Croucher
Multiple myeloma is a plasma cell cancer that develops in the skeleton causing profound bone destruction and fractures. The bone disease is mediated by increased osteoclastic bone resorption and suppressed bone formation. Treatment with bisphosphonates, which inhibit bone resorption, prevents bone loss but fail to influence bone formation and do not replace lost bone, so patients continue to fracture. Stimulating bone formation to increase bone mass and fracture resistance is a priority; however, targeting tumor-derived modulators of bone formation has had limited success...
May 17, 2017: Blood
https://www.readbyqxmd.com/read/28513889/mechanically-induced-bone-formation-is-not-sensitive-to-local-osteocyte-density-in-rat-vertebral-cancellous-bone
#14
Erin N Cresswell, Thu M Nguyen, Michael W Horsfield, Adrian J Alepuz, Thomas A Metzger, Glen L Niebur, Christopher J Hernandez
Osteocytes play an integral role in bone by sensing mechanical stimuli and releasing signaling factors that direct bone formation. The importance of osteocytes in mechanotransduction suggests that regions of bone tissue with greater osteocyte populations are more responsive to mechanical stimuli. To determine the effects of osteocyte population on bone functional adaptation we applied mechanical loads to the 8(th) caudal vertebra of skeletally mature female Sprague Dawley rats (6 months of age, n = 8 loaded, n = 8 sham controls)...
May 17, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28508073/three-dimensional-system-enabling-the-maintenance-and-directed-differentiation-of-pluripotent-stem-cells-under-defined-conditions
#15
Denise Zujur, Kosuke Kanke, Alexander C Lichtler, Hironori Hojo, Ung-Il Chung, Shinsuke Ohba
The development of in vitro models for the maintenance and differentiation of pluripotent stem cells (PSCs) is an active area of stem cell research. The strategies used so far are based mainly on two-dimensional (2D) cultures, in which cellular phenotypes are regulated by soluble factors. We show that a 3D culture system with atelocollagen porous scaffolds can significantly improve the outcome of the current platforms intended for the maintenance and lineage specification of mouse PSCs (mPSCs). Unlike 2D conditions, the 3D conditions maintained the undifferentiated state of mouse embryonic stem cells (mESCs) without exogenous stimulation and also supported endoderm, mesoderm, and ectoderm differentiation of mESCs under serum-free conditions...
May 2017: Science Advances
https://www.readbyqxmd.com/read/28507207/role-of-osteocytes-in-mediating-bone-mineralization-during-hyperhomocysteinemia
#16
Viji Vijayan, Sarika Gupta
Hyperhomocysteinemia (HHCY) is a risk factor for osteoporosis but whether HHCY affects bone mineralization or not is still ambiguous. Herein we evaluated whether homocysteine affects tissue mineral density (TMD) of cortical bone and if so the role of osteocytes. CD1 mice administered with homocysteine (5 mg/100 g body weight, i.p.) for 7, 15 and 30 days showed temporal changes in TMD and osteocyte lacunar density in femoral cortices. Short-term administration of homocysteine (day 7) increased osteocyte lacunar density and reduced TMD evidenced by microCT50 while prolonged administration of homocysteine (day 30) reinstated TMD and lacunar density to baseline values...
June 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28503340/administration-frequency-as-well-as-dosage-of-pth-are-associated-with-development-of-cortical-porosity-in-ovariectomized-rats
#17
Aya Takakura, Ji-Won Lee, Kyoko Hirano, Yukihiro Isogai, Toshinori Ishizuya, Ryoko Takao-Kawabata, Tadahiro Iimura
To investigate whether the administration frequency of parathyroid hormone (PTH) is associated with the development of cortical porosity, this study established 15 dosage regimens of teriparatide [human PTH(1-34), TPTD] with four distinct concentrations and four distinct administration frequencies of TPTD to 16-week-old ovariectomized rats. Our analyses demonstrated that the bone mineral density, mechanical properties, and bone turnover were associated with the total amount of TPTD administered. Our observations further revealed that the cortical porosity was markedly developed as a result of an increased administration frequency with a lower concentration of total TPTD administration in our setting, although the highest concentration also induced cortical porosity...
2017: Bone Research
https://www.readbyqxmd.com/read/28501301/osteocyte-dysfunction-and-renal-osteodystrophy-not-just-calcium-and-phosphorus-anymore
#18
Katherine Wesseling-Perry
In an important new cross-sectional analysis in this issue, Graciolli and colleagues present bone data from 148 adult patients across the spectrum of chronic kidney disease that confirm that disrupted osteocyte function and abnormal bone histology characterize all stages of chronic kidney disease and suggest that osteocytic Wnt signaling and osteocyte maturation may play a role in the pathogenesis of renal osteodystrophy. These concepts may alter how the skeletal, cardiovascular, and infectious complications of chronic kidney disease are managed...
June 2017: Kidney International
https://www.readbyqxmd.com/read/28494043/maxillary-sinus-floor-augmentation-using-xenograft-gene-expression-and-histologic-analysis
#19
Jaijam Suwanwela, Dollaya Puangchaipruk, Kamolporn Wattanasirmkit, Paksinee Kamolratanakul, Pornchai Jansisyanont
PURPOSE: Many histologic and histomorphometric studies as well as systematic reviews have shown the clinical success of the use of anorganic bovine bone (ABB, Bio-Oss) in maxillary sinus floor augmentation (MSFA). The molecular processes involved in bone healing are, however, still unknown. The aims of this study were to explore gene expression associated with bone remodeling and inflammation in MSFA sites. MATERIALS AND METHODS: The mRNA expression levels of runt related transcription factor 2 (RUNX2), receptor activator of NF-kB ligand (RANKL), osteoprotegerin (OPG), matrix metallopeptidase 9 (MMP-9), tartrate-resistance acid phosphatase (TRAP), and interleukin-1beta (IL-1β), as well as the ratio of RANKL/OPG were compared between alveolar bone of a group after MSFA with ABB and a maxillary posterior edentulous bone group...
May 2017: International Journal of Oral & Maxillofacial Implants
https://www.readbyqxmd.com/read/28492981/evidence-that-osteocytes-in-autogenous-bone-fragments-can-repair-disrupted-canalicular-networks-and-connect-with-osteocytes-in-de-novo-formed-bone-on-the-fragment-surface
#20
Furqan A Shah, Anders Palmquist
Autogenous bone fragments generated during surgery (e.g. implant site preparation) accelerate bone formation by the release of a large variety of growth factors from the extracellular matrix and the cells contained within. Osteocytes, whether viable or apoptotic, within such fragments are able to recruit osteoclasts to a site of bone remodelling. Here, using correlative scanning electron microscopy, we provide compelling evidence that at one week healing in the Sprague Dawley rat tibia, following surgery (and/or the placement of a bone-anchored implant), autogenous bone fragments support bone formation on their surface...
May 10, 2017: Calcified Tissue International
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