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Sclerostin

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https://www.readbyqxmd.com/read/27918899/the-effects-of-sost-on-implant-osseointegration-in-ovariectomy-osteoporotic-mice
#1
Rui Shu, Dongqing Ai, Ding Bai, Jinlin Song, Mengyuan Zhao, Xianglong Han
OBJECTIVE: Osteoporosis is a risk factor for implant fixation failure. The inhibition of sclerostin effectively improves bone formation and bone remodeling. Therefore, this study investigated whether SOST deficiency enhances the osseointegration of implants in a mouse model of osteoporosis induced by ovariectomy (OVX). DESIGN: Osteoporosis was induced in female C57BL/6 and SOST deficient mice by OVX. Titanium implants were placed in the bilateral distal aspects of the femurs...
November 21, 2016: Archives of Oral Biology
https://www.readbyqxmd.com/read/27888435/increased-sclerostin-and-bone-turnover-after-diet-induced-weight-loss-in-type-2-diabetes-a-post-hoc-analysis-of-the-madiab-trial
#2
Rocky Strollo, Andreea Soare, Yeganeh Manon Khazrai, Antonio Di Mauro, Andrea Palermo, Rossella Del Toro, Sara Fallucca, Maria Giovanna Belluomo, Laura Dugo, Mario Pianesi, Paolo Pozzilli, Nicola Napoli
BACKGROUND: Sclerostin has been directly related to bone turnover increase in dietary-induced weight loss in non-diabetics. This has not been studied in type 2 diabetes, a condition characterized by increased circulating sclerostin and impaired bone turnover. PURPOSE: To study the effect of dietary weight loss and quality of the dietary intervention on changes of sclerostin and bone turnover markers in type 2 diabetes. METHODS: This was a post-hoc analysis of the MADIAB trial, a 21-day randomized controlled trial on overweight/obese type 2 diabetes patients...
November 25, 2016: Endocrine
https://www.readbyqxmd.com/read/27888056/sclerostin-expression-and-functions-beyond-the-osteocyte
#3
Megan M Weivoda, Stephanie J Youssef, Merry Jo Oursler
Sclerostin, the product of the SOST gene, is a secreted inhibitor of Wnt signaling that is produced by osteocytes to regulate bone formation. While it is often considered an osteocyte-specific protein, SOST expression has been reported in numerous other cell types, including hypertrophic chondrocytes and cementocytes. Of interest, SOST/sclerostin expression is altered in certain pathogenic conditions, including osteoarthritis and rheumatic joint disease, and it is unclear whether sclerostin plays a protective role or whether sclerostin may mediate disease pathogenesis...
November 22, 2016: Bone
https://www.readbyqxmd.com/read/27885183/-osteoporosis-and-mechano-biosciences
#4
Toshio Matsumoto
Mechanical unloading due to long-term bedrest or microgravity during spaceflight causes a devastating influence on bone. Although bisphosphonates can prevent bone loss and hypercalciuria by mechanical unloading for up to 6 months, the influence of unloading for longer period of time is unknown. This is because mechanical loading is one of the most important stimuli for bone formation. Mechanical stress activates several intracellular signaling pathways. Among them, activation of stress-activated cation channel by fluid shear stress stimulates ERK-CREB signaling to enhance the expression of fos family transcription factors, which stimulates IL-11 expression in osteoblastic cells...
2016: Clinical Calcium
https://www.readbyqxmd.com/read/27865001/romosozumab-improves-bone-mass-and-strength-while-maintaining-bone-quality-in-ovariectomized-cynomolgus-monkeys
#5
Michael S Ominsky, Steven K Boyd, Aurore Varela, Jacquelin Jolette, Melanie Felx, Nancy Doyle, Nacera Mellal, Susan Y Smith, Kathrin Locher, Sabina Buntich, Ian Pyrah, Rogely W Boyce
Romosozumab (Romo), a humanized sclerostin antibody, is a bone-forming agent under development for treatment of osteoporosis. To examine the effects of Romo on bone quality, mature cynomolgus monkeys (cynos) were treated 4 months post-ovariectomy (OVX) with vehicle, 3, or 30 mg/kg Romo for 12 months, or with 30 mg/kg Romo for 6 months followed by vehicle for 6 months (30/0). Serum bone formation markers were increased by Romo during the first 6 months, corresponding to increased cancellous, endocortical, and periosteal bone formation in rib and iliac biopsies at months 3 and 6...
November 10, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/27862326/sclerostin-antibody-administration-converts-bone-lining-cells-into-active-osteoblasts
#6
Sang Wan Kim, Yanhui Lu, Elizabeth A Williams, Forest Lai, Ji Yeon Lee, Tetsuya Enishi, Deepak H Balani, Michael S Ominsky, Hua Zhu Ke, Henry M Kronenberg, Marc N Wein
Sclerostin antibody (Scl-Ab) increases osteoblast activity, in part through increasing modeling-based bone formation on previously quiescent surfaces. Histomorphometric studies have suggested that this might occur through conversion of bone lining cells into active osteoblasts. However, direct data demonstrating Scl-Ab-induced conversion of lining cells into active osteoblasts is lacking. Here, we used in vivo lineage tracing to determine if Scl-Ab promotes the conversion of lining cells into osteoblasts on periosteal and endocortical bone surfaces in mice...
November 14, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/27861654/preliminary-findings-on-the-role-of-sclerostin-in-the-osseointegration-process-around-titanium-implants
#7
Fábio Luiz da Silva, Carlos Alberto Alves Maced, Daiane Cristina Peruzzo, Victor Angelo Montalli, Poliana Mendes Duarte, Marcelo Henrique Napimoga
PURPOSE: Studies have recognized the importance of Wnt/β-catenin signals in osteoblastogenesis. Sclerostin is a glycoprotein product of the SOST gene that inhibits Wnt/β-catenin signaling and reduces osteoblastogenesis. To date, there is little evidence regarding the role of the Wnt/β-catenin pathway and its inhibitors in the osseointegration process. Therefore, the aim of this study was to evaluate the expression of sclerostin in bone healing around titanium implants inserted in rats...
November 2016: International Journal of Oral & Maxillofacial Implants
https://www.readbyqxmd.com/read/27846800/treatment-with-cinacalcet-increases-plasma-sclerostin-concentration-in-hemodialysis-patients-with-secondary-hyperparathyroidism
#8
Piotr Kuczera, Marcin Adamczak, Andrzej Więcek
BACKGROUND: Sclerostin is a paracrine acting factor, which is expressed in the osteocytes and articular chondrocytes. Sclerostin decreases the osteoblast-related bone formation through the inhibition of the Wnt/β-catenin pathway. Osteocytes also express the Calcium sensing receptor which is a target for cinacalcet. The aim of this study was to assess the influence of six-month cinacalcet treatment on plasma sclerostin concentration in hemodialysed patients with secondary hyperparathyroidism (sHPT)...
November 15, 2016: BMC Nephrology
https://www.readbyqxmd.com/read/27837171/preventing-painful-age-related-bone-fractures-anti-sclerostin-therapy-builds-cortical-bone-and-increases-the-proliferation-of-osteogenic-cells-in-the-periosteum-of-the-geriatric-mouse-femur
#9
Michelle L Thompson, Stephane R Chartier, Stefanie A Mitchell, Patrick W Mantyh
Age-related bone fractures are usually painful and have highly negative effects on a geriatric patient's functional status, quality of life, and survival. Currently, there are few analgesic therapies that fully control bone fracture pain in the elderly without significant unwanted side effects. However, another way of controlling age-related fracture pain would be to preemptively administer an osteo-anabolic agent to geriatric patients with high risk of fracture, so as to build new cortical bone and prevent the fracture from occurring...
2016: Molecular Pain
https://www.readbyqxmd.com/read/27832985/effects-of-raloxifene-against-letrozole-induced-bone-loss-in-chemically-induced-model-of-menopause-in-mice
#10
Abul Kalam, Sushama Talegaonkar, Divya Vohora
INTRODUCTION: The deleterious effects of letrozole, an aromatase inhibitor, used in the adjuvant treatment of breast cancer in postmenopausal women, on bone are well-documented and represent a major drawback to its clinical use. Raloxifene, a selective estrogen receptor modulator and a clinically approved anti-osteoporotic drug, has been recently demonstrated to be efficacious in women with breast cancer. The present study evaluated the effects of preventive and curative treatment with raloxifene on letrozole-induced alterations of bone microarchitecture and turnover markers in a chemically-induced menopause model in mice...
November 8, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27796463/defining-the-properties-of-an-array-of-nh2-modified-substrates-for-the-induction-of-a-mature-osteoblast-osteocyte-phenotype-from-a-primary-human-osteoblast-population-using-controlled-nanotopography-and-surface-chemistry
#11
Sandra A Fawcett, Judith M Curran, Rui Chen, Nicholas P Rhodes, Mark F Murphy, Peter Wilson, Lakshminarayan Ranganath, Jane P Dillon, James A Gallagher, John A Hunt
Accelerating the integration of a joint replacement or the healing of a bone fracture, particularly a complicated non-union fracture, would improve patient welfare and decrease healthcare costs. Currently, an autologous bone graft is the gold standard method for the treatment of complicated non-union fractures, but it is not always possible to harvest such a graft. A proactive highly inductive so-called smart material approach is pertinent in these cases. In this study, the surface chemistry of a previously approved material with desirable bulk material properties was modified to investigate its potential as an economical and effective alternative...
October 28, 2016: Calcified Tissue International
https://www.readbyqxmd.com/read/27796050/inflammatory-bowel-disease-in-a-rodent-model-alters-osteocyte-protein-levels-controlling-bone-turnover
#12
Corinne E Metzger, A Narayanan, D C Zawieja, S A Bloomfield
Bone loss is a common comorbidity of inflammatory bowel disease (IBD), leading to elevated fracture risk in these patients. Inflammatory factors associated with IBD cause increased bone resorption and decreased bone formation with multiple factors implicated as instigators of these alterations. In this project, we examined the influence of IBD on osteocytes proteins in male rats (2 months old) divided into two groups: induced gut inflammation via TNBS enema and vehicle control. We examined the prevalence of two pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), an anti-inflammatory cytokine, interleukin-10 (IL-10), the anabolic factor insulin-like growth factor-I (IGF-I), osteoclastogenesis regulators RANKL and OPG, and the bone formation inhibitor sclerostin in osteocytes in three bone compartments 4 weeks after initiation of gut inflammation...
October 31, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/27789417/effects-of-sclerostin-antibodies-in-animal-models-of-osteoporosis
#13
Michael Stuart Ominsky, Rogely Waite Boyce, Xiaodong Li, Hua Zhu Ke
There is an unmet need for therapies that can restore bone strength and reduce fracture risk among patients at high risk of osteoporotic fracture. To address this need, bone-forming therapies that increase osteoblast activity are required to help restore bone structure and strength. Sclerostin is now recognized as a target for osteoporosis therapy. Sclerostin is predominantly secreted by the osteocyte and acts as an extracellular inhibitor of canonical Wnt signaling by binding to the receptors lipoprotein receptor-related protein-4, 5 and 6...
October 24, 2016: Bone
https://www.readbyqxmd.com/read/27787773/bone-metabolism-in-patients-with-anorexia-nervosa-and-amenorrhoea
#14
L Idolazzi, M El Ghoch, R Dalle Grave, P V Bazzani, S Calugi, S Fassio, C Caimmi, O Viapiana, F Bertoldo, V Braga, M Rossini, D Gatti
PURPOSE: Aim of this study is focusing on bone metabolism in AN patients with amenorrhoea and related estrogen deficiency effects. METHODS: AN patients were compared both with healthy females and with postmenopausal women (reference model for estrogen deficiency). The study sample included 81 females with AN. Laboratory tests [25-OH vitamin D, bone turnover markers, intact parathyroid hormone, sclerostin (SOST) and dickkopf-related protein (DKK1)] and dual energy X-ray absorptiometry (DXA) were taken into account...
October 27, 2016: Eating and Weight Disorders: EWD
https://www.readbyqxmd.com/read/27780792/application-of-anti-sclerostin-therapy-in-non-osteoporosis-disease-models
#15
Christina M Jacobsen
Sclerostin, a known inhibitor of the low density lipoprotein related protein 5 and 6 (LRP5 and LRP6) cell surface signaling receptors, is integral in the maintenance of normal bone mass and strength. Patients with loss of function mutations in SOST or missense mutations in LRP5 that prevent Sclerostin from binding and inhibiting the receptor, have significantly increased bone mass. This observation leads to the development of Sclerostin neutralizing therapies to increase bone mass and strength. Anti-Sclerostin therapy has been shown to be effective at increasing bone density and strength in animal models and patients with osteoporosis...
October 22, 2016: Bone
https://www.readbyqxmd.com/read/27776451/lutein-a-carotenoid-suppresses-osteoclastic-bone-resorption-and-stimulates-bone-formation-in-cultures
#16
Tsukasa Tominari, Chiho Matsumoto, Kenta Watanabe, Michiko Hirata, Florian M W Grundler, Masaki Inada, Chisato Miyaura
Lutein, a member of the xanthophyll family of carotenoids, suppressed IL-1-induced osteoclast differentiation and bone resorption. The survival of mature osteoclasts was also suppressed by lutein in cultures. When lutein was added to the cultures of osteoblasts, lutein enhanced the formation of mineralized bone nodules by elevating BMP2 expression and inhibiting sclerostin expression. Lutein may be beneficial for bone health.
October 25, 2016: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/27774939/-knockdown-of-sost-in-mda-mb-231-breast-cancer-cells-increase-mg-63-osteoblast-like-cell-function-in-co-culture-system
#17
Junxiong Cheng, Dan Guo, Xi Chen, Ting Wang, Jiayi Huang
Objective To construct a recombinant adenovirus expressing siRNA targeting human sclerostin (SOST) gene, and test the function of MG-63 cells while co-cultured with MDA-MB-231 cells infected by Ad-siSOST. MethodsAccording to the RNA sequence of SOST gene, two pairs of primers which contained 3 siRNA sequences were designed, and a pB2B plasmid was taken as template to amplify 2 DNA sequences. Both of the 2 DNA sequences were ligated to pAdTrace-OK by Gibson DNA Assembly way. After homologous recombination between recombinant shuttle plasmid and adenovirus vector plasmid, the adenovirus was packaged in HEK-293 cells...
November 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/27772732/corrigendum-to-lower-uncarboxylated-osteocalcin-and-higher-sclerostin-levels-are-significantly-associated-with-coronary-artery-disease-bone-83-2016-178-183
#18
Kyoung Min Kim, Soo Lim, Jae Hoon Moon, Hyunjin Jin, Kyong Yeun Jung, Chan Soo Shin, Kyong Soo Park, Hak Chul Jang, Sung Hee Choi
No abstract text is available yet for this article.
December 2016: Bone
https://www.readbyqxmd.com/read/27771382/transcriptional-control-of-sost-in-bone
#19
Aimy Sebastian, Gabriela G Loots
Sclerostin is an osteocyte derived negative regulator of bone formation. A highly specific expression pattern and the exclusive bone phenotype have made Sclerostin an attractive target for therapeutic intervention in treating metabolic bone diseases such as osteoporosis and in facilitating fracture repair. Understanding the molecular mechanisms that regulate Sclerostin transcription is of great interest as it may unveil new avenues for therapeutic approaches. Such studies may also elucidate how various signaling pathways intersect to modulate bone metabolism...
October 19, 2016: Bone
https://www.readbyqxmd.com/read/27766367/increased-levels-of-dickkopf-1-are-indicative-of-wnt-%C3%AE-catenin-downregulation-and-lower-osteoblast-signaling-in-children-and-adolescents-with-type-1-diabetes-mellitus-contributing-to-lower-bone-mineral-density
#20
C Tsentidis, D Gourgiotis, L Kossiva, A Marmarinos, A Doulgeraki, K Karavanaki
: Higher levels of Dickkopf-1, which is an inhibitor of Wnt/β-catenin bone metabolic pathway, could be indicative of downregulated Wnt system, with possible lower osteoblast activation and higher osteoclast signaling in type 1 diabetes mellitus children and adolescents. Dickkopf-1 could significantly contribute to diabetes osteopathy. INTRODUCTION: Increased fracture risk and elevated Dickkopf-1 levels, which is an inhibitor of Wnt/β-catenin bone metabolic pathway, have been documented in adult patients with type 2 diabetes mellitus (T2D), while no relevant data exist on childhood type 1 diabetes (T1D)...
October 20, 2016: Osteoporosis International
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