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https://www.readbyqxmd.com/read/29774401/high-levels-of-serum-sclerostin-and-dkk1-in-a-case-of-klippel-tr%C3%A3-naunay-syndrome
#1
P Muto, A Lo Gullo, G Mandraffino, S Loddo, M Atteritano
Klippel-Trénaunay syndrome (KTS) is described as a complex syndrome characterized by various combinations of capillary, venous, and lymphatic malformations associated with bone and soft tissue hypertrophy. We report a case of a 67-year-old postmenopausal Caucasian women with KTS that shows elevated levels of sclerostin and Dickkopf-related protein 1 (DKK1). Dual-energy X-ray absorptiometry (DXA) BMD T-scores at lumbar spine and femur were normal. Serum calcium and phosphorus levels were consistently normal, 25-hydroxyvitamin D (25OHD) < 30 ng/mL, and normal parathyroid hormone (PTH)...
May 17, 2018: Osteoporosis International
https://www.readbyqxmd.com/read/29758362/the-anti-epileptic-drugs-valproate-carbamazepine-and-levetiracetam-cause-bone-loss-and-modulate-wnt-inhibitors-in-normal-and-ovariectomised-rats
#2
Bushra Parveen, Ambrish Kumar Tiwari, Moon Jain, Subhashis Pal, Naibedya Chattopadhyay, Manjari Tripathi, Divya Vohora
Secondary osteoporosis is the major concern associated with long term intake of antiepileptic drugs (AEDs). Women are the vulnerable targets owing to post-menopausal bone loss. In the present work, we evaluated the effect of 10 weeks of treatment with AED therapy (carbamazepine, CBZ, 75 mg/kg; sodium valproate, SVP, 300 mg/kg; levetiracetam, LTM, 150 mg/kg) on bone mineral density and microarchitecture at femoral epiphysis, lumbar vertebrae and proximal tibia of normal and ovariectomised Wistar rats...
May 11, 2018: Bone
https://www.readbyqxmd.com/read/29753194/targeting-wnt-signaling-in-the-treatment-of-osteoporosis
#3
REVIEW
Roland Baron, Francesca Gori
Osteoporosis is a widespread chronic disease characterized by low bone density, altered microstructure and bone fragility, leading to low impact fractures in affected individuals. The discovery of a few mutations that cause extremely rare human diseases has identified the WNT signaling pathway as a candidate for therapeutic intervention aimed at increasing bone mass and strength. In particular, inhibition of sclerostin, a WNT antagonist secreted by osteocytes, has proven in clinical trials to be a very efficient osteo-anabolic approach...
May 9, 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29750826/conditional-deletion-of-sost-in-msc-derived-lineages-identifies-specific-cell-type-contributions-to-bone-mass-and-b-cell-development
#4
Cristal S Yee, Jennifer O Manilay, Jiun C Chang, Nicholas R Hum, Deepa K Murugesh, Jamila Bajwa, Melanie E Mendez, Aris E Economides, Daniel J Horan, Alexander G Robling, Gabriela G Loots
Sclerostin (Sost) is a negative regulator of bone formation and blocking its function via antibodies has shown great therapeutic promise by increasing both bone mass in humans and animal models. Sclerostin deletion in Sost knockout mice (Sost-/- ) causes high bone mass (HBM) similar to Sclerosteosis patients. Sost-/- mice have been shown to display an up to 300% increase in bone volume/total volume (BV/TV), relative to aged matched controls, and it has been postulated that the main source of skeletal Sclerostin is the osteocyte...
May 11, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/29746861/lenalidomide-regulates-osteocytes-fate-and-related-osteoclastogenesis-via-il-1%C3%AE-nf-%C3%AE%C2%BAb-rankl-signaling
#5
Xinhua Qu, Jingtian Mei, Zhifeng Yu, Zanjing Zhai, Han Qiao, Kerong Dai
Osteolytic diseases are closely associated with osteocyte fate, indicating a more efficient and crucial role of osteocyte-targeting strategy in inhibiting osteoclastogenesis. Here, we investigated the effects of lenalidomide (Lena) on osteocyte fate in order to regulate osteoclastogenesis via effective cascade-controlling response. Our data revealed that lenalidomide treatment notably rescued IL-1β induced loss of osteocyte viability by inhibiting osteocyte apoptosis with decreased osteoclast-related factors, RANKL and Sclerostin, as demonstrated by the restricted osteoclast formation and reduced bone resorption...
May 7, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29734465/postnatal-skeletal-deletion-of-dickkopf-1-increases-bone-formation-and-bone-volume-in-male-and-female-mice-despite-increased-sclerostin-expression
#6
Juliane Colditz, Sylvia Thiele, Ulrike Baschant, Christof Niehrs, Lynda F Bonewald, Lorenz C Hofbauer, Martina Rauner
The Wnt antagonist Dickkopf-1 (Dkk1) is a negative regulator of osteoblast function and bone mass. However, due to the lack of appropriate models, many aspects of its role in the regulation of postnatal bone turnover and its cellular source have remained unknown. In this study, we deleted Dkk1 postnatally and in different cell types using various Cre-drivers (Rosa26-ERT2-Cre, Osx-cre,Dmp1-Cre) and assessed to which extent cells of the osteoblastic lineage contribute to the effects of Dkk1 on bone turnover and homeostasis...
May 7, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/29733407/bone-inflammation-and-the-bone-marrow-niche-in-chronic-kidney-disease-what-do-we-know
#7
Sandro Mazzaferro, Giuseppe Cianciolo, Antonio De Pascalis, Chiara Guglielmo, Pablo A Urena Torres, Jordi Bover, Lida Tartaglione, Marzia Pasquali, Gaetano La Manna
Recent improvements in our understanding of physiology have altered the way in which bone is perceived: no longer is it considered as simply the repository of divalent ions, but rather as a sophisticated endocrine organ with potential extraskeletal effects. Indeed, a number of pathologic conditions involving bone in different ways can now be reconsidered from a bone-centred perspective. For example, in metabolic bone diseases like osteoporosis (OP) and renal osteodystrophy (ROD), the association with a worse cardiovascular outcome can be tentatively explained by the possible derangements of three recently discovered bone hormones (osteocalcin, fibroblast growth factor 23 and sclerostin) and a bone-specific enzyme (alkaline phosphatase)...
May 4, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29725706/abaloparatide-exerts-bone-anabolic-effects-with-less-stimulation-of-bone-resorption-related-factors-a-comparison-with-teriparatide
#8
Akito Makino, Hideko Takagi, Yoshimasa Takahashi, Naoki Hase, Hiroyuki Sugiyama, Kei Yamana, Tsunefumi Kobayashi
Abaloparatide (ABL) is a novel synthetic peptide analog of parathyroid hormone-related protein. In previous reports, intermittent ABL administration showed robust bone mineral density (BMD) increase and reduced the incidence of fractures in patients with osteoporosis, while its calcemic effect was reduced, as compared with teriparatide (TPTD), a parathyroid hormone N-terminal fragment. The present study aimed to elucidate the effects of ABL on bone anabolism and bone turnover as compared with TPTD. In ovariectomized (OVX) rats, ABL increased the bone strength and BMD of lumbar spine by intermittent administration similar to TPTD...
May 3, 2018: Calcified Tissue International
https://www.readbyqxmd.com/read/29719588/effects-of-repeated-sprints-training-on-fracture-risk-associated-mirna
#9
Veronica Sansoni, Silvia Perego, Gianluca Vernillo, Andrea Barbuti, Giampiero Merati, Antonio La Torre, Giuseppe Banfi, Giovanni Lombardi
Repeated-sprint training (RS, short-duration sprints at supramaximal intensities interspersed with brief recoveries) is a time-saving metabolically effective strategy whose effects on bone are unknown. Bone metabolism is a finely regulated process profoundly affected by exercise as assayable by studying specific systemic (e.g., hormones, cytokines) and bone-derived molecules (e.g., bone markers, miRNAs). Aim of this study was to determine the effect of a 8-week repeated-sprint on circulating levels of fracture risk-associated miRNA...
April 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29709620/changes-in-tibial-bone-microarchitecture-in-female-recruits-in-response-to-8-weeks-of-u-s-army-basic-combat-training
#10
Julie M Hughes, Erin Gaffney-Stomberg, Katelyn I Guerriere, Kathryn M Taylor, Kristin L Popp, Chun Xu, Ginu Unnikrishnan, Jeffery S Staab, Ronald W Matheny, James P McClung, Jaques Reifman, Mary L Bouxsein
BACKGROUND: U.S. Army Basic Combat Training (BCT) is a physically-demanding program at the start of military service. Whereas animal studies have shown that increased mechanical loading rapidly alters bone structure, there is limited evidence of changes in bone density and structure in humans exposed to a brief period of unaccustomed physical activity. PURPOSE: We aimed to characterize changes in tibial bone density and microarchitecture and serum-based biochemical markers of bone metabolism in female recruits as a result of 8 weeks of BCT...
April 27, 2018: Bone
https://www.readbyqxmd.com/read/29701175/sclerostin-is-not-associated-with-cardiovascular-event-or-fracture-in-kidney-transplantation-candidates
#11
Hanne Skou Jørgensen, Simon Winther, Laust Dupont, Morten Bøttcher, Lars Rejnmark, Ellen-Margrethe Hauge, My Svensson, Per Ivarsen
BACKGROUND: Sclerostin, a bone-derived protein, has been linked to cardiovascular calcifications in chronic kidney disease (CKD). The aim of this study was to investigate the associations between sclerostin and mineral and bone disorder in CKD, specifically whether sclerostin levels could predict cardiovascular event, fracture, or all-cause mortality. MATERIALS AND METHODS: Kidney transplantation candidates (n = 157) underwent computed tomography scans of the chest, abdomen, and pelvis...
April 27, 2018: Clinical Nephrology
https://www.readbyqxmd.com/read/29694950/is-sclerostin-level-associated-with-cardiovascular-diseases-in-hemodialysis-patients
#12
Gokce Kundakci Gelir, Sule Sengul, Gokhan Nergizoglu, Sehsuvar Ertürk, Neval Duman, Sim Kutlay
BACKGROUND/AIMS: The objective of this study is to evaluate the relation between sclerostin, arterial stiffness, and cardiovascular events (CVE) in hemodialysis patients (HD). METHODS: Sclerostin level and carotid-femoral pulse wave velocity (PWV) in 97 HD patients and sclerostin level in 40 controls were measured. RESULTS: Sclerostin level was significantly higher in patients than in controls. Sclerostin associated positively with age, male gender, cardiovascular disease, statin use, BMI, and PWV while negatively with alkaline phosphatase, parathormone (PTH), Kt/V, cinacalcet and vitamin D use in univariable correlation analyses...
April 25, 2018: Blood Purification
https://www.readbyqxmd.com/read/29694687/sclerostin-neutralizing-antibody-treatment-enhances-bone-formation-but-does-not-rescue-mechanically-induced-delayed-healing
#13
Bettina Kruck, Elizabeth A Zimmermann, Sophie Damerow, Christine Figge, Catherine Julien, Dag Wulstein, Tobias Thiele, Madge Martin, Reggie Hamdy, Marie K Reumann, Georg N Duda, Sara Checa, Bettina M Willie
During bone healing, tissue formation processes are governed by mechanical strain. Sost/sclerostin, a key Wnt signaling inhibitor and mechano-sensitive pathway, is downregulated in response to mechanical loading. Sclerostin neutralizing antibody (SclAb) increases bone formation. Nevertheless, it remains unclear whether sclerostin inhibition can rescue bone healing in situations of mechanical instability, which otherwise delay healing. We investigated SclAb's influence on tissue formation in a mouse femoral osteotomy, stabilized with Rigid or Semi-rigid external fixation...
April 25, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/29691807/glucocorticoid-induced-osteoporosis-an-update
#14
REVIEW
Juliet Compston
Glucocorticoid-induced osteoporosis is the most common secondary cause of osteoporosis and the resulting fractures cause significant morbidity. Following initiation of oral glucocorticoids, rapid bone loss occurs, and fracture risk increases within a few months in a dose-dependent manner. These adverse effects are due to inhibition of bone formation accompanied by an early but transient increase in bone resorption. Multiple mechanisms underlie these changes in bone remodeling; direct effects include upregulation of PPARγR2, increased expression of sclerostin and increased RANKL/OPG ratio, whilst hypogonadism, altered renal and intestinal calcium handling, and reduced production of insulin-like growth factor 1 also contribute...
April 24, 2018: Endocrine
https://www.readbyqxmd.com/read/29687585/bone-another-potential-target-to-treat-prevent-and-predict-diabetes
#15
REVIEW
Dong-Mei Liu, Ioanna Mosialou, Jian-Min Liu
Type 2 diabetes mellitus is now a worldwide health problem with increasing prevalence. Mounting efforts have been made to treat, prevent and predict this chronic disease. In recent years, increasing evidence from mice and clinical studies suggest that bone-derived molecules modulate glucose metabolism. This review aims to summarize our current understanding of the interplay between bone and glucose metabolism and highlight potential new means for therapeutic intervention. The first molecule recognized as a link between bone and glucose metabolism in mice is osteocalcin, which functions in its active form, i...
April 23, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29683771/wnt-signaling-related-osteokines-at-rest-and-following-plyometric-exercise-in-prepubertal-and-early-pubertal-boys-and-girls
#16
Panagiota Klentrou, Kirina Angrish, Nafisa Awadia, Nigel Kurgan, Rozalia Kouvelioti, Bareket Falk
PURPOSE: This study examined osteokines related to Wnt signaling at rest and in response to plyometric exercise in 12 boys [10.2 (0.4) y] and 12 girls [10.5 (0.4) y]. METHODS: One resting (preexercise) and 3 postexercise (5 min, 1 h, and 24 h) blood samples were analyzed for sclerostin, dickkopf-related protein 1 (DKK-1), osteoprotegerin (OPG), and receptor activator of nuclear factor kappa-β ligand (RANKL). RESULTS: Girls had higher resting sclerostin than boys [187...
April 23, 2018: Pediatric Exercise Science
https://www.readbyqxmd.com/read/29669893/-sost-deficiency-leads-to-reduced-mechanical-strains-at-the-tibia-midshaft-in-strain-matched-in-vivo-loading-experiments-in-mice
#17
Laia Albiol, Myriam Cilla, David Pflanz, Ina Kramer, Michaela Kneissel, Georg N Duda, Bettina M Willie, Sara Checa
Sclerostin, a product of the Sost gene, is a Wnt-inhibitor and thus negatively regulates bone accrual. Canonical Wnt/β-catenin signalling is also known to be activated in mechanotransduction. Sclerostin neutralizing antibodies are being tested in ongoing clinical trials to target osteoporosis and osteogenesis imperfecta but their interaction with mechanical stimuli on bone formation remains unclear. Sost knockout (KO) mice were examined to gain insight into how long-term Sost deficiency alters the local mechanical environment within the bone...
April 2018: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/29658328/effects-of-enoxaparin-on-intravascular-sclerostin-release-in-healthy-men
#18
Jacek Borawski, Justyna Zoltko, Barbara Labij-Reduta, Ewa Koc-Zorawska, Beata Naumnik
Sclerostin (Scl) is implicated in vascular calcification and angiogenesis and localizes within vasculature. Its molecule incorporates a heparin-binding site that implies also binding to endothelial glycocalyx. We preliminary tested whether intravenous (IV) low-molecular-weight heparin enoxaparin can stimulate intravascular release of this calcification inhibitor in humans. Sixteen male volunteers were injected with a bolus of 1 mg/kg body weight of enoxaparin. After 10 minutes, plasma immunoreactive Scl levels increased uniformly by a mean of 184% versus baseline level of 0...
January 1, 2018: Journal of Cardiovascular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29653294/sclerostin-vaccination-mitigates-estrogen-deficiency-induction-of-bone-mass-loss-and-microstructure-deterioration
#19
Feng-Sheng Wang, Re-Wen Wu, Wei-Shiung Lain, Tsai-Chen Tsai, Yu-Shan Chen, Yi-Chih Sun, Huei-Jing Ke, Jui-Chen Li, Jau-Lang Hwang, Jih-Yang Ko
Sclerostin (SOST) is a Wnt signaling inhibitor detrimental to osteogenic differentiation and bone mineral acquisition. While control of SOST action delays the pathogenesis of skeletal disorders, the effects of SOST vaccination on the estrogen deficiency-induced bone deterioration remain elusive. In this study, we generated a SOST-Fc fusion protein which was composed of a SOST peptide Pro-Asn-Ala-Ile-Gly along with an IgG Fc fragment. SOST-Fc vaccination increased serum anti-SOST antibody levels and reduced serum SOST concentrations in mice...
April 10, 2018: Bone
https://www.readbyqxmd.com/read/29649633/circulating-wnt-inhibitory-factor-1-levels-are-associated-with-development-of-cardiovascular-disease
#20
Claudia Ress, Mariya Paulweber, Georg Goebel, Karin Willeit, Kerstin Rufinatscha, Anna Strobl, Karin Salzmann, Ludmilla Kedenko, Alexander Tschoner, Gabriele Staudacher, Bernhard Iglseder, Herbert Tilg, Bernhard Paulweber, Susanne Kaser
BACKGROUND AND AIMS: Wnt signaling is involved in atherosclerotic plaque formation directly and indirectly by modulating cardiovascular risk factors. We investigated whether circulating concentrations of Wnt inhibitors are associated with cardiovascular events in subjects with intermediate cardiovascular risk. METHODS: 904 non-diabetic subjects participating in the SAPHIR study were assessed. In the SAPHIR study, middle-aged women without overt atherosclerotic disease at study entry were followed up for 10 years...
March 29, 2018: Atherosclerosis
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