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Sclerostin

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https://www.readbyqxmd.com/read/28212706/sclerostin-antibody-inhibits-skeletal-deterioration-in-mice-exposed-to-partial-weight-bearing
#1
J M Spatz, R Ellman, A M Cloutier, L Louis, M van Vliet, D Dwyer, M Stolina, H Z Ke, M L Bouxsein
Whereas much is known regarding the musculoskeletal responses to full unloading, little is known about the physiological effects and response to pharmacological agents in partial unloading (e.g. Moon and Mars) environments. To address this, we used a previously developed ground-based model of partial weight-bearing (PWB) that allows chronic exposure to reduced weight-bearing in mice to determine the effects of murine sclerostin antibody (SclAbII) on bone microstructure and strength across different levels of mechanical unloading...
February 2017: Life Sciences in Space Research
https://www.readbyqxmd.com/read/28184001/igfbp-4-regulates-adult-skeletal-growth-in-a-sex-specific-manner
#2
David E Maridas, Victoria E DeMambro, Phuong T Le, Subburaman Mohan, Cliff Rosen
Insulin-like growth factor-1 (IGF-1) and its binding proteins are critical mediators of skeletal growth. Insulin-like Growth Factor Binding Protein 4 (IGFBP-4) is highly expressed in osteoblasts and inhibits IGF-1 actions in vitro. Yet, in vivo studies suggest that it could potentiate IGF-1 and IGF-2 actions. In this study, we hypothesized that IGFBP-4 might potentiate the actions of IGF-1 on the skeleton. To test this, we comprehensively studied 8 and 16-week-old Igfbp4-/- mice. Both male and female adult Igfbp4-/- mice had marked growth retardation with reductions in body weight, body and femur lengths, fat proportion and lean mass at 8 and 16 weeks...
February 9, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28159704/effects-of-targeted-therapies-on-the-bone-in-arthritides
#3
REVIEW
Ágnes Szentpétery, Ágnes Horváth, Katalin Gulyás, Zsófia Pethö, Harjit Pal Bhattoa, Sándor Szántó, Gabriella Szücs, Oliver FitzGerald, Georg Schett, Zoltán Szekanecz
Inflammatory arthritides, such as rheumatoid arthritis (RA) and spondyloarthritides (SpA) have been associated with both localized bone resorption and/or formation, and generalized osteoporosis. Systemic inflammation may be the major driver for bone loss in arthritis. In RA and peripheral SpA the RANK-RANKL-OPG network is involved in bone resorption, while in axial SpA the Wnt-β-catenin axis and its inhibitors (DKK-1, sclerostin) are the most relevant. Targeted therapies including biologics and small molecule tyrosine kinase inhibitors may interfere with inflammatory bone metabolism...
January 31, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/28153008/correlation-of-blood-bone-turnover-biomarkers-and-wnt-signaling-antagonists-with-as-dish-opll-and-oyl
#4
Chi-Chien Niu, Song-Shu Lin, Li-Jen Yuan, Lih-Huei Chen, Chuen-Yung Yang, An-Ni Chung, Meng-Ling Lu, Tsung-Ting Tsai, Po-Liang Lai, Wen-Jer Chen
BACKGROUND: Wnt signaling plays an important role in development and maintenance of many organs and tissues. The most-studied secreted Wnt inhibitors are sclerostin (SOST), Dickkopf-related protein 1 (DKK-1), and secreted frizzled related protein 1 (SFRP-1) which play important roles in bone turnover. The present study investigated the relationship between serum Wnt inhibitors and diseases with excessive ossification structures, such as ossification of posterior longitudinal ligament (OPLL), ankylosing spondylitis (AS), diffuse idiopathic skeletal hyperostosis (DISH), and ossification of yellow ligament (OYL)...
February 2, 2017: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/28138749/the-relationship-between-postmenopausal-women-s-sclerostin-levels-and-their-bone-density-age-body-mass-index-hormonal-status-and-smoking-and-consumption-of-coffee-and-dairy-products
#5
Muberra Namlı Kalem, Ziya Kalem, Nilufer Akgun, Batuhan Bakırarar
PURPOSE: To investigate the relationship between postmenopausal women's sclerostin levels and bone density and the factors that may affect this relationship. MATERIALS AND METHODS: 135 postmenopausal patients' ages, BMIs, hormonal statuses, BMD values, and smoking, and consumption of coffee and dairy products were compared with their sclerostin levels. RESULTS: No statistical relationship was found between sclerostin level and age in the group with osteoporosis (p = 0...
January 31, 2017: Archives of Gynecology and Obstetrics
https://www.readbyqxmd.com/read/28134398/-new-biomarkers-of-ckd-mbd
#6
Marzia Pasquali, Lida Tartaglione, Silverio Rotondi
Chronic kidney failure involves abnormalities of mineral metabolism, skeletal and of cardiovascular system (so called CKD - MBD) that have a major impact on the survival of renal patient. Increasingly complex pathophysiological mechanisms have been discovered in recent years with evidence of new molecules involved in the development of CKD - MBD. Besides the classical PTH / Vitamin D axis, the most recent discovery of a new FGF23 / Klotho axis has expanded knowledge on the mechanisms of mineral homeostasis but also on the more complex mechanisms of cellular aging, vascular calcification and cardiac remodeling...
November 2016: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
https://www.readbyqxmd.com/read/28132908/administration-of-an-activin-receptor-iib-ligand-trap-protects-male-juvenile-rhesus-macaques-from-simian-immunodeficiency-virus-associated-bone-loss
#7
Wen Guo, Karol M Pencina, Karyn O'Connell, Monty Montano, Liming Peng, Susan Westmoreland, Julie Glowacki, Shalender Bhasin
: HIV-infected individuals are at an increased risk of osteoporosis despite effective viral suppression. Observations that myostatin null mice have increased bone mass led us to hypothesize that simian immunodeficiency virus (SIV)-associated bone loss may be attenuated by blocking myostatin/TGFβ signaling. In this proof-of-concept study, pair-housed juvenile male rhesus macaques were inoculated with SIVmac239. Four weeks later, animals were treated with vehicle or Fc-conjugated soluble activin receptor IIB (ActR2B·Fc, iv...
January 26, 2017: Bone
https://www.readbyqxmd.com/read/28115281/clinical-utility-of-anti-sclerostin-antibodies
#8
Michael R McClung
Based on a platform of strong preclinical data, several studies in humans have demonstrated that inhibiting sclerostin with specific antibodies results in a brisk albeit transient anabolic response in the skeleton without an accompanying increase in bone resorption. Impressive increases in bone mineral density and bone strength have been demonstrated. Other than mild injection site reactions, therapy for up to 2years has been well tolerated. The restriction of sclerostin expression almost exclusively to skeletal tissues, coupled with the absence of recognized medical problems in patients with heterozygous sclerostin deficiency, provides promise that the drug can be used safely...
January 20, 2017: Bone
https://www.readbyqxmd.com/read/28115280/sclerostin-from-bedside-to-bench-and-back-to-bedside
#9
EDITORIAL
Alexander G Robling, Matthew T Drake, Socrates E Papapoulos
No abstract text is available yet for this article.
January 20, 2017: Bone
https://www.readbyqxmd.com/read/28092987/emerging-treatment-approaches-for-myeloma-related-bone-disease
#10
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/28091892/bariatric-roux-en-y-gastric-bypass-surgery-adipocyte-proteins-involved-in-increased-bone-remodeling-in-humans
#11
Maria Fernanda G Biagioni, Adriana L Mendes, Célia Regina Nogueira, Celso V Leite, Loraine Gollino, Gláucia Mfs Mazeto
PURPOSE: Bariatric surgery has been associated with bone remodeling changes. The action of adipokines on the expression of receptor activator of nuclear factor kappa β ligand (RANKL) and osteoprotegerin (OPG) and on an increase in sclerostin could be related to these changes. MATERIALS AND METHODS: This study aimed to assess the repercussions of weight loss, fat mass (FM), and fat-free mass (FFM) loss and biochemical and hormonal changes on bone remodeling markers after Roux-en-Y gastric bypass (RYGB)...
January 13, 2017: Obesity Surgery
https://www.readbyqxmd.com/read/28090669/the-association-between-sclerostin-and-incident-type-2-diabetes-risk-a-cohort-study
#12
Oriana Hoi Yun Yu, Brent Richards, Claudie Berger, Robert G Josse, William D Leslie, David Goltzman, Stephanie M Kaiser, Christopher S Kovacs, K Shawn Davison
OBJECTIVE: To determine whether sclerostin is associated with fasting glucose, insulin levels, insulin resistance or increased risk of incident type 2 diabetes. BACKGROUND: Type 2 diabetic patients have a higher risk of fractures. Recent studies suggest sclerostin, a regulator of osteoblast activity, is associated with diabetes. MATERIALS AND METHODS: Sclerostin levels were obtained from 1,778 individuals with no history of type 2 diabetes participating in the population-based Canadian Multicentre Osteoporosis Study (CaMos) cohort...
January 15, 2017: Clinical Endocrinology
https://www.readbyqxmd.com/read/28081119/sclerostin-promotes-bone-remodeling-in-the-process-of-tooth-movement
#13
Rui Shu, Ding Bai, Tzongjen Sheu, Yao He, Xianrui Yang, Chaoran Xue, Yiruo He, Mengyuan Zhao, Xianglong Han
Tooth movement is a biological process of bone remodeling induced by mechanical force. Sclerostin secreted by osteocytes is mechanosensory and important in bone remodeling. However, little is known regarding the role of sclerostin in tooth movement. In this study, models of experimental tooth movement were established in rats and mice. Sclerostin expression was investigated with immunohistochemistry staining, and osteoclastic activity was analyzed with tartrate-resistant acid phosphatase (TRAP) staining. MLO-Y4 osteocyte-like cells underwent uniaxial compression and tension stress or were cultured in hypoxia conditions...
2017: PloS One
https://www.readbyqxmd.com/read/28078875/circulating-srage-in-the-diagnosis-of-osteolytic-bone-metastasis
#14
E Galliera, M G Marazzi, E Vianello, L Drago, A Luzzati, P Bendinelli, P Maroni, L Tacchini, M A Desiderio, M M Corsi Romanelli
Despite the clinical importance of metastasis to the skeleton, the diagnostic tools for early detection and monitoring of bone metastasis lack sensitivity and specificity. We evaluated a promising new serum biomarker, the soluble form of the Receptor of Advanced Glycosylated End-products (sRAGE). sRAGE is involved in the Wnt-signaling pathway, and has been reported to reduce the risk of cancer. We investigated the diagnostic potential of sRAGE to improve the detection and monitoring of bone metastasis. We measured sRAGE in the serum of control healthy subjects, patients with primary tumors and patients with bone metastasis...
October 2016: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28064540/romosozumab-for-the-treatment-of-osteoporosis
#15
Leonardo Bandeira, E Michael Lewiecki, John P Bilezikian
Sclerostin, a glycoprotein produced primarily by osteocytes, blocks the canonical Wnt signaling bone formation pathway. Romosozumab is a humanized monoclonal antibody to sclerostin that binds to sclerostin, permitting the engagement of Wnt ligands with their co-receptors, resulting in an increase in bone formation and bone mineral density (BMD). Clinical studies with romosozumab have shown dramatic improvements in BMD at the spine and hip. Romosozumab is associated with improvement in bone strength through mechanisms that include increases in bone formation and, different from classical osteoanabolic agents, suppression of bone resorption...
February 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28062506/wnt-signaling-pathway-inhibitor-sclerostin-inhibits-angiotensin-ii-induced-aortic-aneurysm-and-atherosclerosis
#16
Smriti Murali Krishna, Sai-Wang Seto, Roby J Jose, Jiaze Li, Susan K Morton, Erik Biros, Yutang Wang, Vianne Nsengiyumva, Jan H N Lindeman, Gabriela G Loots, Catherine M Rush, Jeffrey M Craig, Jonathan Golledge
OBJECTIVE: Sclerostin (SOST) has been identified as an important regulator of bone formation; however, it has not been previously implicated in arterial disease. The aim of this study was to assess the role of SOST in aortic aneurysm (AA) and atherosclerosis using human samples, a mouse model, and in vitro investigations. APPROACH AND RESULTS: SOST protein was downregulated in human and mouse AA samples compared with controls. Transgenic introduction of human SOST in apolipoprotein E-deficient (ApoE(-/-)) mice (SOST(Tg)...
December 22, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28054585/osseous-differentiation-of-human-fat-tissue-grafts-from-tissue-engineering-to-tissue-differentiation
#17
Maryna Bondarava, Chiara Cattaneo, Bin Ren, Wolfgang E Thasler, Volkmar Jansson, Peter E Müller, Oliver B Betz
Conventional bone tissue engineering approaches require isolation and in vitro propagation of autologous cells, followed by seeding on a variety of scaffolds. Those protracted procedures impede the clinical applications. Here we report the transdifferentiation of human fat tissue fragments retrieved from subcutaneous fat into tissue with bone characteristics in vitro without prior cell isolation and propagation. 3D collagen-I cultures of human fat tissue were cultivated either in growth medium or in osteogenic medium (OM) with or without addition of Bone Morphogenetic Proteins (BMPs) BMP-2, BMP-7 or BMP-9...
January 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28054306/circulating-dickkopf-1-and-sclerostin-in-patients-with-paget-s-disease-of-bone
#18
Luca Idolazzi, Angelo Fassio, Gaia Tripi, Vania Braga, Ombretta Viapiana, Giovanni Adami, Maurizio Rossini, Davide Gatti
Paget disease of bone is a chronic metabolic bone disorder characterized by increased bone resorption and new bone formation. The aim of this study is defining the role of inhibitors of canonical Wnt/b-catenin signaling pathway in patients with Paget disease of bone. Scarce and contrasting results have been reported in literature. We studied 40 patients (15 females and 25 males) with radiological and scintigraphic evidence of Paget disease of bone and 40 healthy subjects matched by age and sex. N-propeptide of type I collagen, C-terminal telopeptide of type I collagen, sclerostin, and Dickkopf-related protein 1 (DKK1) were evaluated by blood samples in our laboratory...
January 5, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28049653/mechanisms-in-endocrinology-diabetes-mellitus-a-state-of-low-bone-turnover-a-systematic-review-and-meta-analysis
#19
REVIEW
Katrine Hygum, Jakob Starup-Linde, Torben Harsløf, Peter Vestergaard, Bente L Langdahl
OBJECTIVE: To investigate the differences in bone turnover between diabetic patients and controls. DESIGN: A systematic review and meta-analysis. METHODS: A literature search was conducted using the databases Medline at PubMed and EMBASE. The free text search terms 'diabetes mellitus' and 'bone turnover', 'sclerostin', 'RANKL', 'osteoprotegerin', 'tartrate-resistant acid' and 'TRAP' were used. Studies were eligible if they investigated bone turnover markers in patients with diabetes compared with controls...
March 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/28030966/systemic-drugs-that-influence-titanium-implant-osseointegration
#20
Dragos Apostu, Ondine Lucaciu, Gheorghe Dan Osvald Lucaciu, Bogdan Crisan, Liana Crisan, Mihaela Baciut, Florin Onisor, Grigore Baciut, Radu Septimiu Câmpian, Simion Bran
Titanium implants are widely used on an increasing number of patients in orthopedic and dental medicine. Despite the good survival rates of these implants, failures that lead to important socio-economic consequences still exist. Recently, research aimed at improving implant fixation, a process called osseointegration, has focused on a new, innovative field: systemic delivery of drugs. Following implant fixation, patients receive systemic drugs that could either impair or enhance osseointegration; these drugs include anabolic and anti-catabolic bone-acting agents in addition to new treatments...
January 23, 2017: Drug Metabolism Reviews
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