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https://www.readbyqxmd.com/read/29353451/analysis-of-circulating-mediators-of-bone-remodeling-in-prader-willi-syndrome
#1
G Brunetti, G Grugni, L Piacente, M Delvecchio, A Ventura, P Giordano, M Grano, G D'Amato, D Laforgia, A Crinò, M F Faienza
We tested the hypothesis that the levels of bone remodeling mediators may be altered in Prader-Willi syndrome (PWS). We assessed RANKL, OPG, sclerostin, DKK-1 serum levels, and bone metabolism markers in 12 PWS children (7.8 ± 4.3 years), 14 PWS adults (29.5 ± 7.2 years), and 31 healthy controls matched for sex and age. Instrumental parameters of bone mineral density (BMD) were also evaluated. Lumbar spine BMD Z-scores were reduced in PWS children (P < 0.01), reaching osteopenic levels in PWS adults...
January 20, 2018: Calcified Tissue International
https://www.readbyqxmd.com/read/29353057/mechanisms-of-enhanced-osteoclastogenesis-in-alkaptonuria
#2
Giacomina Brunetti, Albina Tummolo, Gabriele D'Amato, Alberto Gaeta, Federica Ortolani, Laura Piacente, Paola Giordano, Silvia Colucci, Maria Grano, Francesco Papadia, Maria Felicia Faienza
Alkaptonuria (AKU) is a rare disorder characterized by the deficiency of the enzyme homogentisate 1,2-dioxygenase and consequent homogentisate accumulation, which leads to progressive and severe osteoarthopathy starting from the second decade of life. Thus, in AKU patients bone involvement represents an important clinical issue, which we investigated. Serum levels of RANKL, osteoprotegerin, sclerostin, DKK1, and bone remodeling markers were measured in nine AKU patients (two children and seven adults) and 22 controls, together with lumbar spine bone mineral density (LS-BMD) and femoral-BMD...
January 15, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29351359/cyr61-ccn1-regulates-sclerostin-levels-and-bone-maintenance
#3
Gexin Zhao, Bau-Lin Huang, Diana Rigueur, Weiguang Wang, Chimay Bhoot, Kemberly R Charles, Jongseung Baek, Subburaman Mohan, Jie Jiang, Karen M Lyons
CYR61/CCN1 is a matricellular protein that resides in the extracellular matrix, but serves regulatory rather than structural roles. CYR61/CCN1 is found in mineralized tissues and has been shown to influence bone healing in vivo and osteogenic differentiation in vitro. In this study we generated Cyr61 bone specific knockout mice to examine the physiological role of CYR61/CCN1 in bone development and maintenance in vivo. Extensive analysis of Cyr61 conditional knockout mice showed a significant decrease in both trabecular and cortical bone mass as compared to WT littermate...
January 19, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/29349060/sost-deficiency-does-not-alter-bone-s-lacunar-or-vascular-porosity-in-mice
#4
Henry Mosey, Juan A Núñez, Alice Goring, Claire E Clarkin, Katherine A Staines, Peter D Lee, Andrew A Pitsillides, Behzad Javaheri
SCLEROSTIN (Sost) is expressed predominantly in osteocytes acting as a negative regulator of bone formation. In humans, mutations in the SOST gene lead to skeletal overgrowth and increased bone mineral density, suggesting that SCLEROSTIN is a key regulator of bone mass. The function of SCLEROSTIN as an inhibitor of bone formation is further supported by Sost knockout (KO) mice which display a high bone mass with elevated bone formation. Previous studies have indicated that Sost exerts its effect on bone formation through Wnt-mediated regulation of osteoblast differentiation, proliferation, and activity...
September 13, 2017: Frontiers in Materials
https://www.readbyqxmd.com/read/29344330/developments-in-rare-bone-diseases-and-mineral-disorders
#5
REVIEW
Siobhan Bacon, Rachel Crowley
In the last decade, there have been a number of significant advances made in the field of rare bone diseases. In this review, we discuss the expansion of the classification system for osteogenesis imperfecta (OI) and the resultant increase in therapeutic options available for management of OI. Bisphosphonates remain the most widely used intervention for OI, although the effect on fracture rate reduction is equivocal. We review the other therapies showing promising results, including denosumab, teriparatide, sclerostin, transforming growth factor β inhibition and gene targeted approaches...
January 2018: Therapeutic Advances in Chronic Disease
https://www.readbyqxmd.com/read/29343193/perinatal-sclerostin-concentrations-in-abnormal-fetal-growth-the-impact-of-gestational-diabetes
#6
Despina D Briana, Maria Boutsikou, Antonios Marmarinos, Dimitrios Gourgiotis, Ariadne Malamitsi-Puchner
OBJECTIVE: To prospectively evaluate maternal and cord blood concentrations of sclerostin -an osteocyte-secreted factor, inhibiting osteoblast differentiation and bone formation and associated with adverse metabolism- in pregnancies with normal and abnormal fetal growth. METHODS: Plasma sclerostin concentrations were determined by ELISA in 80 maternal and 80 cord blood samples from asymmetric intrauterine-growth-restricted (IUGR, n = 30), large-for-gestational-age (LGA, n = 30) and appropriate-for-gestational-age (AGA, n = 20) singleton full-term pregnancies...
January 17, 2018: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/29331722/effect-of-vitamin-d-supplementation-on-serum-sclerostin-levels-in-chronic-kidney-disease
#7
REVIEW
Ashok Kumar Yadav, Vivek Kumar, Debasish Banerjee, Krishan Lal Gupta, Vivekanand Jha
Vitamin D deficiency, cardiovascular disease and abnormal bone mineral metabolism are common in chronic kidney disease (CKD). Abnormal bone mineral metabolism has been linked to vascular calcification in CKD. Sclerostin has emerged as an important messenger in cross talk between bone-vascular axis. We analyzed sclerostin in subjects who participated in the randomized, double blind, placebo controlled trial investigating the effect of cholecalciferol supplementation on vascular function in non-diabetic CKD stage G3-4 and vitamin D ≤20ng/ml [CTRI/2013/05/003648]...
January 10, 2018: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29307778/computational-and-functional-characterization-of-four-snps-in-the-sost-locus-associated-with-osteoporosis
#8
Weiyuan Ye, Ya Wang, Bing Mei, Sasa Hou, Xinhong Liu, Guiju Wu, Longjuan Qin, Kehui Zhao, Qingyang Huang
The SOST gene encodes sclerostin, a C-terminal cysteine knot-like domain containing key negative regulator of osteoblastic bone formation that inhibits LRP5/6-mediated canonical Wnt signaling. Numerous single nucleotide polymorphisms (SNPs) in the SOST locus are firmly associated with bone mineral density (BMD) and fracture in genome-wide association studies (GWAS) and candidate gene association studies. However, the validation and mechanistic elucidation of causal genetic variants, especially for SNPs located beyond the promoter-proximal region, remain largely unresolved...
January 4, 2018: Bone
https://www.readbyqxmd.com/read/29303699/implication-of-osteoprotegerin-and-sclerostin-in-axial-spondyloarthritis-cardiovascular-disease-study-of-163-spanish-patients
#9
Fernanda Genre, Javier Rueda-Gotor, Sara Remuzgo-Martínez, Alfonso Corrales, Begoña Ubilla, Verónica Mijares, Carlos Fernández-Díaz, Virginia Portilla, Ricardo Blanco, José Luis Hernández, Javier Llorca, Raquel López-Mejías, Miguel Angel González-Gay
OBJECTIVES: Due to the high incidence of cardiovascular disease in axial spondyloarthritis (axSpA), the search of potential biomarkers that may help to identify patients with high cardiovascular risk is of main importance. Therefore, in this study we assessed the implication of osteoprotegerin (OPG) and sclerostin (SCL), two biomarkers associated with cardiovascular disease and bone metabolism, in the clinical spectrum and atherosclerotic disease of patients with axSpA. METHODS: OPG and SCL serum levels were determined in 163 axSpA Spanish patients (119 ankylosing spondylitis and 44 non-radiographic axSpA) and 63 healthy controls by enzyme-linked immunosorbent assay...
December 15, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/29290007/bone-geometry-quality-and-bone-markers-in-children-with-type-1-diabetes-mellitus
#10
Roberto Franceschi, Silvia Longhi, Vittoria Cauvin, Angelo Fassio, Giuseppe Gallo, Fiorenzo Lupi, Petra Reinstadler, Antonio Fanolla, Davide Gatti, Giorgio Radetti
Adults with Type 1 diabetes mellitus show a high risk of bone fracture, probably as a consequence of a decreased bone mass and microarchitectural bone alterations. The aim of the study was to investigate the potential negative effects of type 1 diabetes on bone geometry, quality, and bone markers in a group of children and adolescents. 96 children, mean age 10.5 ± 3.1 years, agreed to participate to the study. Bone geometry was evaluated on digitalized X-rays at the level of the 2nd metacarpal bone. The following parameters were investigated and expressed as SDS: outer diameter (D), inner diameter (d), cortical area (CA), and medullary area (MA)...
December 30, 2017: Calcified Tissue International
https://www.readbyqxmd.com/read/29279421/-bone-derived-hormones-and-their-systemic-regulation
#11
Yuichi Takashi, Seiji Fukumoto, Toshio Matsumoto
Bone has several functions such as supporting our body, protecting internal organs and contributing to hematopoiesis. Recently, it has been revealed that bone also works as an endocrine tissue and systemically regulates functions of other organs. It has been reported that fibroblast growth factor 23(FGF23)regulates phosphate metabolism and osteocalcin affect glucose/energy metabolism. In addition, sclerostin, interleukin-11(IL-11)and lipocalin 2 have been also found to be bone-derived humoral factors. Further investigation concerning the network systems among multiple organs via bone-derived hormones may lead to the development of new drugs...
2018: Clinical Calcium
https://www.readbyqxmd.com/read/29243300/antagonists-of-wnt-%C3%AE-catenin-signaling-in-the-periodontitis-associated-with-type-2-diabetes-and-smoking
#12
Tamires Szeremeske Miranda, Marcelo Henrique Napimoga, Magda Feres, Letícia Macedo Marins, Daniele Ferreira da Cruz, Hélio Doyle Pereira da Silva, Poliana Mendes Duarte
AIM: This study evaluated the levels of sclerostin (SOST) and Dickkopf (DKK)-1 in the chronic periodontitis (CP) associated with type 2 diabetes (DM) and/or smoking. Relationships between SOST, DDK1, RANKL, OPG, IL-1ß, IL-6 and TNF-α, and pathogens were assessed. MATERIAL AND METHODS: The study population included non-diabetic non-smokers (control), non-smokers with DM (DM group), non-diabetic smokers (S group) and smokers with DM (SDM group), all with CP. Serum and gingival levels of SOST, DKK1, RANKL, OPG, IL-1ß, IL-6, and TNF-α were evaluated by multiplex immunoassay...
December 15, 2017: Journal of Clinical Periodontology
https://www.readbyqxmd.com/read/29240821/tumor-necrosis-factor-%C3%AE-antagonist-diminishes-osteocytic-rankl-and-sclerostin-expression-in-diabetes-rats-with-periodontitis
#13
Ji-Hye Kim, Ae Ri Kim, Yun Hui Choi, Sungil Jang, Gye-Hyeong Woo, Jeong-Heon Cha, Eun-Jung Bak, Yun-Jung Yoo
Type 1 diabetes with periodontitis shows elevated TNF-α expression. Tumor necrosis factor (TNF)-α stimulates the expression of receptor activator of nuclear factor-κB ligand (RANKL) and sclerostin. The objective of this study was to determine the effect of TNF-α expression of osteocytic RANKL and sclerostin in type 1 diabetes rats with periodontitis using infliximab (IFX), a TNF-α antagonist. Rats were divided into two timepoint groups: day 3 and day 20. Each timepoint group was then divided into four subgroups: 1) control (C, n = 6 for each time point); 2) periodontitis (P, n = 6 for each time point); 3) diabetes with periodontitis (DP, n = 8 for each time point); and 4) diabetes with periodontitis treated with IFX (DP+IFX, n = 8 for each time point)...
2017: PloS One
https://www.readbyqxmd.com/read/29229807/sclerostin-influences-body-composition-by-regulating-catabolic-and-anabolic-metabolism-in-adipocytes
#14
Soohyun P Kim, Julie L Frey, Zhu Li, Priyanka Kushwaha, Meredith L Zoch, Ryan E Tomlinson, Hao Da, Susan Aja, Hye Lim Noh, Jason K Kim, Mehboob A Hussain, Daniel L J Thorek, Michael J Wolfgang, Ryan C Riddle
Sclerostin has traditionally been thought of as a local inhibitor of bone acquisition that antagonizes the profound osteoanabolic capacity of activated Wnt/β-catenin signaling, but serum sclerostin levels in humans exhibit a correlation with impairments in several metabolic parameters. These data, together with the increased production of sclerostin in mouse models of type 2 diabetes, suggest an endocrine function. To determine whether sclerostin contributes to the coordination of whole-body metabolism, we examined body composition, glucose homeostasis, and fatty acid metabolism in Sost-/- mice as well as mice that overproduce sclerostin as a result of adeno-associated virus expression from the liver...
December 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29226516/sost-an-lngfr-target-inhibits-the-osteogenic-differentiation-of-rat-ectomesenchymal-stem-cells
#15
Gang Li, Junyu Liu, Manzhu Zhao, Yingying Wang, Kun Yang, Chang Liu, Yong Xiao, Xiujie Wen, Luchuan Liu
OBJECTIVES: The aim of this study was to investigate whether sclerostin (SOST) regulates the osteogenic differentiation of rat ectomesenchymal stem cells (EMSCs) and whether SOST and low-affinity nerve growth factor receptor (LNGFR) regulate the osteogenic differentiation of EMSCs. MATERIALS AND METHODS: EMSCs were isolated from embryonic facial processes from an embryonic 12.5-day (E12.5d) pregnant Sprague-Dawley rat. LNGFR+ EMSCs and LNGFR- EMSCs were obtained by fluorescence-activated cell sorting and were subsequently induced to undergo osteogenic differentiation in vitro...
December 10, 2017: Cell Proliferation
https://www.readbyqxmd.com/read/29197633/spondyloarthritis-features-in-zymosan-induced-skg-mice
#16
Hyemin Jeong, Eun-Kyung Bae, Hunnyun Kim, Dong Hui Lim, Tae-Young Chung, Jaejoon Lee, Chan Hong Jeon, Eun-Mi Koh, Hoon-Suk Cha
OBJECTIVES: Spondyloarthritis (SpA) encompasses a group of disorders including ankylosing spondylitis, psoriatic arthritis, reactive arthritis, and enteropathic arthritis. SpA pathogenesis is still not well understood. Animal models are important for studying disease mechanisms and identifying new therapeutic agents. Recently, a β-glucan-induced SKG mouse was used as an animal model for SpA. The aim of this study was to evaluate the clinical and molecular characteristics of a zymosan-induced SKG mouse...
November 29, 2017: Joint, Bone, Spine: Revue du Rhumatisme
https://www.readbyqxmd.com/read/29194852/the-role-of-sclerostin-dickkopf-1-and-receptor-activator-of-nuclear-factor-kb-ligand-osteoprotegerin-signalling-pathways-in-the-development-of-osteoporosis-in-patients-with-haemophilia-a-and-b-a-cross-sectional-study
#17
P Anagnostis, S Vakalopoulou, D Christoulas, S A Paschou, A Papatheodorou, V Garipidou, P Kokkoris, E Terpos
AIM: Haemophilia A and B are associated with reduced bone mineral density (BMD). The aim of this study was to assess circulating sclerostin and dickkopf-1 (Dkk-1), (inhibitors of osteoblastic differentiation), as well as the receptor activator of nuclear factor kB ligand (RANKL)/osteoprotegerin (OPG) system (the major regulator of osteoclastogenesis), in patients with haemophilia (PWH), their possible correlations with clinical risk factors and the effect of ibandronate on these markers...
December 1, 2017: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://www.readbyqxmd.com/read/29194725/levels-of-serum-sclerostin-metabolic-parameters-and-periodontitis-in-postmenopausal-women-with-diabetes
#18
Roberto Carlos Mourão Pinho, Larissa Bastos Pimentel, Francisco Alfredo Farias Bandeira, Rayanne Soraia Aguiar Melo Dias, Renata Cimões
Diabetes mellitus (DM) is a metabolic disease defined by hyperglycemia, which is associated with periodontal disease and exerts an effect on bone metabolism. The aim of this study was to determine serum levels of sclerostin in postmenopausal women with diabetes and determine a possible association with periodontal disease. Sixty-one postmenopausal women (32 with diabetes and 29 without diabetes) were evaluated. Blood was collected for biochemical analysis and the determination of serum sclerostin. The participants were also submitted to a clinical examination for the evaluation of periodontal status...
December 1, 2017: Special Care in Dentistry
https://www.readbyqxmd.com/read/29192796/the-effect-of-weight-loss-on-body-composition-serum-bone-markers-and-adipokines-in-prepubertal-obese-children-after-1-year-intervention
#19
Joanna Gajewska, Jadwiga Ambroszkiewicz, Witold Klemarczyk, Magdalena Chełchowska, Halina Weker, Katarzyna Szamotulska
Purpose/Aim: The influence of weight loss on bone turnover and bone quality in childhood remains controversial, but it may implicate interactions between adiposity and bone metabolism. Therefore, we studied the relationships between bone markers and adipokines during weight loss in obese children. MATERIALS AND METHODS: We determined serum leptin, soluble leptin receptor, adiponectin, bone alkaline phosphatase (BALP), C-terminal telopeptide of type I collagen (CTX-I), osteocalcin (OC), carboxylated-OC (Gla-OC), undercarboxylated-OC (Glu-OC), sclerostin, body composition, and bone mineral density (BMD) in 40 obese prepubertal children before and after therapy...
December 1, 2017: Endocrine Research
https://www.readbyqxmd.com/read/29187373/klotho-activin-a-in-kidney-injury-plasma-klotho-is-maintained-in-unilateral-obstruction-despite-no-upregulation-of-klotho-biosynthesis-in-contralateral-kidney
#20
Anders Nordholm, Maria L Mace, Eva Gravesen, Jacob Hofman-Bang, Marya Morevati, Klaus Olgaard, Ewa Lewin
In a new paradigm of etiology related to Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) kidney injury may cause induction of factors in the injured kidney that are released into the circulation and thereby initiate and maintain renal fibrosis and CKD-MBD. Klotho is believed to ameliorate renal fibrosis and CKD-MBD, while ActivinA might have detrimental effects. The unilateral ureter obstruction (UUO) model is used here to examine this concept by investigating early changes related to renal fibrosis in obstructed kidney, untouched contralateral kidney and vasculature, which might be affected by secreted factors from the obstructed kidney, and compared to unilateral nephrectomized controls (UNX)...
November 29, 2017: American Journal of Physiology. Renal Physiology
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