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Sclerostin

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https://www.readbyqxmd.com/read/28341377/lrp5-from-bedside-to-bench-to-bone
#1
Bart O Williams
A role for Low-density lipoprotein related receptor 5 (LRP5) in human bone was first established by the identification of genetic alterations that led to dramatic changes in human bone mass. Shortly thereafter, mutations that altered the function of the Sclerostin (SOST) gene were also associated with altered human bone mass. Subsequent studies of LRP5 and Sclerostin have provided important insights into the mechanisms by which these proteins regulate skeletal homeostasis. Sclerostin normally binds to LRP5 and the related LRP6 protein and prevents their activation by Wnt ligands...
March 21, 2017: Bone
https://www.readbyqxmd.com/read/28339088/sclerostin-is-a-possible-candidate-marker-of-arterial-stiffness-results-from-a-cohort-study-in-catania
#2
Agostino Gaudio, Valerio Fiore, Rosario Rapisarda, Maria Helga Sidoti, Anastasia Xourafa, Antonino Catalano, Giovanni Tringali, Luca Zanoli, Salvatore Santo Signorelli, Carmelo Erio Fiore
Osteoporosis and cardiovascular disease are worldwide public health issues. Recent evidence indicates a possible role of the canonical Wnt/β-catenin signalling pathway as a common mediator between these two diseases. The aim of the present study was to investigate the relationship between serum concentrations of sclerostin and Dkk1, two extracellular inhibitors of Wnt/β-catenin signalling, with carotid intima-media thickness (CIMT) and with arterial stiffness, evaluated by measuring the pulse wave velocity (PWV) in an ambulatory population of adults...
March 24, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28338087/gs%C3%AE-controls-cortical-bone-quality-by-regulating-osteoclast-differentiation-via-camp-pka-and-%C3%AE-catenin-pathways
#3
Girish Ramaswamy, Hyunsoo Kim, Deyu Zhang, Vitali Lounev, Joy Y Wu, Yongwon Choi, Frederick S Kaplan, Robert J Pignolo, Eileen M Shore
Skeletal bone formation and maintenance requires coordinate functions of several cell types, including bone forming osteoblasts and bone resorbing osteoclasts. Gsα, the stimulatory subunit of heterotrimeric G proteins, activates downstream signaling through cAMP and plays important roles in skeletal development by regulating osteoblast differentiation. Here, we demonstrate that Gsα signaling also regulates osteoclast differentiation during bone modeling and remodeling. Gnas, the gene encoding Gsα, is imprinted...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28332354/cyclized-oligopeptide-targeting-lrp5-6-dkk1-interaction-reduces-the-growth-of-tumor-burden-in-a-multiple-myeloma-mouse-model
#4
Bo Mi Park, Eun Jin Kim, Hee Jin Nam, Dongdong Zhang, Chu Hyun Bae, Myeongmo Kang, Heeyoun Kim, Weontae Lee, Bjarne Bogen, Sung Kil Lim
PURPOSE: Dickkopf 1 (DKK1) has been extensively investigated in mouse models of multiple myeloma, which results in osteolytic bone lesions. Elevated DKK1 levels in bone marrow plasma and serum inhibit the differentiation of osteoblast precursors. Present pharmaceutical approaches to target bone lesions are limited to antiresorptive agents. In this study, we developed a cyclized oligopeptide against DKK1-low density lipoprotein receptor-related protein (LRP) 5/6 interaction and tested the effects of the oligopeptide on tumor burden...
May 2017: Yonsei Medical Journal
https://www.readbyqxmd.com/read/28326342/short-term-intermittent-administration-of-parathyroid-hormone-facilitates-osteogenesis-by-different-mechanisms-in-cancellous-and-cortical-bone
#5
Kenji Ogura, Tadahiro Iimura, Yuji Makino, Ayano Sugie-Oya, Aya Takakura, Ryoko Takao-Kawabata, Toshinori Ishizuya, Keiji Moriyama, Akira Yamaguchi
Intermittent administration of human parathyroid hormone (1-34)[hPTH(1-34)] induces anabolic action on the bones. To understand the mechanism underlying the early phase of hPTH(1-34)-induced anabolic action, we investigated the expression profiles of osterix and sclerostin after short-term intermittent administration of hPTH(1-34) using immunohistochemistry in adult rats. In the cancellous bone, hPTH(1-34) administration greatly increased the number of osterix-positive cells in the bone marrow on day 1, but the cells gradually decreased on days 3 and 5...
December 2016: Bone Reports
https://www.readbyqxmd.com/read/28323146/hypogonadal-men-with-type-2-diabetes-mellitus-have-smaller-bone-size-and-lower-bone-turnover
#6
Georgia Colleluori, Lina Aguirre, Richard Dorin, David Robbins, Dean Blevins, Yoann Barnouin, Rui Chen, Clifford Qualls, Dennis T Villareal, Reina Armamento-Villareal
INTRODUCTION: Both hypogonadism and type 2 diabetes mellitus (T2D) are associated with increased fracture risk. Emerging data support the negative effect of low testosterone on glucose metabolism, however, there is little information on the bone health of hypogonadal men with diabetes. We evaluated the bone mineral density (BMD), bone geometry and bone turnover of hypogonadal men with T2D compared to hypogonadal men without diabetes. MATERIALS AND METHODS: Cross-sectional study, men 40-74years old, with average morning testosterone (done twice) of<300ng/dl...
March 16, 2017: Bone
https://www.readbyqxmd.com/read/28323143/effect-of-age-and-gender-on-serum-periostin-relationship-to-cortical-measures-bone-turnover-and-hormones
#7
Jennifer S Walsh, Fatma Gossiel, Jessica R Scott, Margaret A Paggiosi, Richard Eastell
Periostin is an extracellular matrix protein, and in bone is expressed most highly in the periosteum. It increases bone formation through osteoblast differentiation, cell adhesion, Wnt signalling and collagen cross-linking. We hypothesised that serum periostin would be high at times of life when cortical modeling is active, in early adulthood and in older age, and that it would correlate with cortical bone measures, bone turnover and hormones that regulate cortical modeling. We conducted a cross-sectional observational study of 166 healthy men and women at three skeletal stages; the end of longitudinal growth (16-18years), peak bone mass (30-32years) and older age (over 70years)...
March 16, 2017: Bone
https://www.readbyqxmd.com/read/28318623/the-complexity-of-chronic-kidney-disease-mineral-and-bone-disorder-across-stages-of-chronic-kidney%C3%A2-disease
#8
Fabiana G Graciolli, Katia R Neves, Fellype Barreto, Daniela V Barreto, Luciene M Dos Reis, Maria E Canziani, Yves Sabbagh, Aluizio B Carvalho, Vanda Jorgetti, Rosilene M Elias, Susan Schiavi, Rosa M A Moysés
Chronic Kidney Disease (CKD)-Mineral and Bone Disorder (CKD-MBD) is a complex disease that is not completely understood. However, some factors secreted by the osteocytes might play an important role in its pathophysiology. Therefore, we evaluated the bone expression of proteins in a group of patients with CKD 2-3, CKD 4, and CKD 5 on dialysis and healthy individuals. We also tested several bone remodeling markers, and correlated these levels with bone biopsy findings. As expected, as serum calcium decreased, serum phosphate, alkaline phosphatase, fibroblast growth factor-23 (FGF-23), parathyroid hormone, and osteoprotegerin increased, as CKD progressed...
March 15, 2017: Kidney International
https://www.readbyqxmd.com/read/28275825/co-expression-of-dkk-1-and-sclerostin-in-subchondral-bone-of-the-proximal-femoral-heads-from-osteoarthritic-hips
#9
Allahdad Zarei, Philippa A Hulley, Afsie Sabokbar, M Kassim Javaid
BACKGROUND: Osteoarthritis (OA) is a progressively degenerative joint disease influenced by structural and metabolic factors. There is growing evidence that subchondral bone is involved in both symptomatic and structural progression in OA. The Wnt pathway has been implicated in the progression of OA but the expression and function of the Wnt inhibitors, Dikkopf (DKK-1) and sclerostin (SOST), are unclear. METHODS: We examined the regional distribution of DKK-1 and SOST in subchondral bone of the femoral head using resection specimens following arthroplasty in patients presenting with end-stage OA...
March 9, 2017: Calcified Tissue International
https://www.readbyqxmd.com/read/28271451/the-utility-of-biomarkers-in-osteoporosis-management
#10
REVIEW
Patrick Garnero
The measurement of bone turnover markers is useful for the clinical investigation of patients with osteoporosis. Among the available biochemical markers, the measurements of serum procollagen type I N-terminal propeptide (PINP) and the crosslinked C-terminal telopeptide (serum CTX) have been recommended as reference markers of bone formation and bone resorption, respectively. The important sources of preanalytical and analytical variability have been identified for both markers, and precise measurement can now be obtained...
March 7, 2017: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/28267633/sclerostin-stimulates-angiogenesis-in-human-endothelial-cells
#11
Angela Oranger, Giacomina Brunetti, Graziana Colaianni, Roberto Tamma, Claudia Carbone, Luciana Lippo, Giorgio Mori, Paolo Pignataro, Nunzio Cirulli, Roberta Zerlotin, Biagio Moretti, Angela Notarnicola, Domenico Ribatti, Maria Grano, Silvia Colucci
Sclerostin, negative regulator of bone formation, has been originally known as an osteocyte product. Recently, it has been also detected in hypertrophic chondrocytes, distinctive cells of avascular cartilage which is invaded by capillaries and then replaced by vascularized bone. Thus, we hypothesized that sclerostin, in addition to its role already known, may exert an angiogenic activity. We first proved that sclerostin increased the proliferation of human umbilical vein endothelial cells (HUVECs), and next, by using the chicken chorioallantoic membrane (CAM) in vivo assay, we demonstrated that it exerts an angiogenic activity similar to that of vascular endothelial growth factor (VEGF)...
March 3, 2017: Bone
https://www.readbyqxmd.com/read/28261616/the-protective-effect-of-chrysanthemum-indicum-extract-against-ankylosing-spondylitis-in-mouse-models
#12
Mei Dong, Dongsheng Yu, Veeramuthu Duraipandiyan, Naif Abdullah Al-Dhabi
In traditional Chinese and Korean homeopathic medicine, Chrysanthemum indicum Linné (Asteraceae) is a time-honored herb, prescribed for the resolution of symptoms associated with inflammatory and hypertensive conditions as well as those affecting the lungs and its associated structures. The goal of this work is to investigate the defensive role of Chrysanthemum indicum extract in fighting ankylosing spondylitis (AS) using mouse models, through which the manifestation and extent of the disease progression were measured with quantitative analysis of the intervertebral joints...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28259981/wnt-%C3%AE-catenin-signaling-pathway-inhibition-by-sclerostin-may-protect-against-degradation-in-healthy-but-not-osteoarthritic-cartilage
#13
Jiang Wu, Long Ma, Long Wu, Qunhua Jin
The aim of the present study was to determine the regulation of sclerostin (SOST) in osteoarthritis (OA) and its effect on articular cartilage degradation. Human cartilage samples from healthy and OA subjects were assessed by Safranin O staining and immunohistochemistry. Primary chondrocytes were pre‑incubated with 250 ng/ml SOST, 10 ng/ml interleukin‑1‑α (IL‑1α) or a combination of the two. The effects of treatment on the Wnt-β-catenin signaling pathway and cartilage degradation were examined by reverse transcription‑quantitative polymerase chain reaction and western blotting...
March 3, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28255336/bone-modeling-and-remodeling-potential-as-therapeutic-targets-for-the-treatment-of-osteoporosis
#14
REVIEW
Bente Langdahl, Serge Ferrari, David W Dempster
The adult skeleton is renewed by remodeling throughout life. Bone remodeling is a process where osteoclasts and osteoblasts work sequentially in the same bone remodeling unit. After the attainment of peak bone mass, bone remodeling is balanced and bone mass is stable for one or two decades until age-related bone loss begins. Age-related bone loss is caused by increases in resorptive activity and reduced bone formation. The relative importance of cortical remodeling increases with age as cancellous bone is lost and remodeling activity in both compartments increases...
December 2016: Therapeutic Advances in Musculoskeletal Disease
https://www.readbyqxmd.com/read/28254365/macrotopographic-closure-promotes-tissue-growth-and-osteogenesis-in-vitro
#15
Laura Juignet, Baptiste Charbonnier, Virginie Dumas, Wafa Bouleftour, Mireille Thomas, Coralie Laurent, Laurence Vico, Nathalie Douard, David Marchat, Luc Malaval
While the impact of substrate topographies at nano- and microscale on bone cell behavior has been particularly well documented, very few studies have analyzed the role of substrate closure at a tissular level. Moreover, these have focused on matrix deposition rather than on osteoblastic differentiation. In the present work, mouse calvaria cells were grown for 15days on hydroxyapatite (HA) ceramics textured with three different macrogrooves shapes ((**)100µm): 1 sine and 2 triangle waveforms. We found that macrotopography favors cell attachment, and that bone-like tissue growth and organization are promoted by a tight "closure angle" of the substrate geometry...
February 22, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28250244/markers-of-bone-metabolism-during-14-days-of-bed-rest-in-young-and-older-men
#16
J Buehlmeier, P Frings-Meuthen, N Mohorko, P Lau, S Mazzucco, J L Ferretti, G Biolo, R Pisot, B Simunic, J Rittweger
OBJECTIVE: We aimed at comparing markers of bone metabolism during unloading in young and older men, and to assess countermeasure effectiveness. METHODS: 16 older (60±2 years) and 8 younger men (23±3 years) underwent bed rest (BR) for 14 days. A subgroup of the Older performed cognitive training during BR and supplemented protein and potassium bicarbonate afterwards. Biochemical markers of bone and calcium/phosphate metabolism were assessed. RESULTS: At baseline urinary NTX and CTX were greater in younger than in older subjects (P<0...
March 1, 2017: Journal of Musculoskeletal & Neuronal Interactions
https://www.readbyqxmd.com/read/28246931/effects-of-sost-gene-silencing-on-proliferation-apoptosis-invasion-and-migration-of-human-osteosarcoma-cells-through-the-wnt-%C3%AE-catenin-signaling-pathway
#17
Jian Zou, Wei Zhang, Xiao-Lin Li
Our study explored the effects of SOST gene silencing on the proliferation, apoptosis, invasion, and migration of human osteosarcoma cells through Wnt/β-catenin signaling pathway. Fresh tissues were obtained from 108 patients with osteosarcoma and 46 patients with osteochondroma. Human osteosarcoma cells (MG-63, U2-OS, HOS, and Saos-2) and normal osteoblast (hFoB1.19) were selected and cultured. Osteosarcoma cells were grouped randomly into the blank group, the scrambled control group, and the SOST-siRNA group...
February 28, 2017: Calcified Tissue International
https://www.readbyqxmd.com/read/28246926/romosozumab-treatment-converts-trabecular-rods-into-trabecular-plates-in-male-cynomolgus-monkeys
#18
Jonathan B Matheny, Ashley M Torres, Michael S Ominsky, Christopher J Hernandez
Treatment with sclerostin antibody (romosozumab) increases bone formation while reducing bone resorption, leading to increases in bone volume and bone mineral density. Sclerostin antibody treatment may also provide beneficial changes in trabecular microarchitecture and strength that are not reflected in bone volume and density. Here we use three-dimensional dynamic histomorphometry to determine longitudinal changes in vertebral trabecular microarchitecture in adolescent male cynomolgus monkeys (4-5 years old) treated with sclerostin antibody...
February 28, 2017: Calcified Tissue International
https://www.readbyqxmd.com/read/28240364/n-cadherin-regulation-of-bone-growth-and-homeostasis-is-osteolineage-stage-specific
#19
Francesca Fontana, Cynthia L Hickman-Brecks, Valerie S Salazar, Leila Revollo, Grazia Abou-Ezzi, Susan K Grimston, Sung Yeop Jeong, Marcus Watkins, Manuela Fortunato, Yael Alippe, Daniel C Link, Gabriel Mbalaviele, Roberto Civitelli
N-cadherin inhibits osteogenic cell differentiation and canonical Wnt/β-catenin signaling in vitro. However, in vivo both conditional Cdh2 ablation and overexpression in osteoblasts lead to low bone mass. We tested the hypothesis that N-cadherin has different effects on osteolineage cells depending upon their differentiation stage. Embryonic conditional osteolineage Cdh2 deletion in mice results in defective growth, low bone mass and reduced osteoprogenitor number. These abnormalities are prevented by delaying Cdh2 ablation until 1 month of age, thus targeting only committed and mature osteoblasts, suggesting they are the consequence of N-cadherin deficiency in osteoprogenitors...
February 27, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28239825/upregulated-serum-sclerostin-level-in-the-t2dm-patients-with-femur-fracture-inhibits-the-expression-of-bone-formation-remodeling-associated-biomarkers-via-antagonizing-wnt-signaling
#20
Y Wu, S-Y Xu, S-Y Liu, L Xu, S-Y Deng, Y-B He, S-C Xian, Y-H Liu, G-X Ni
OBJECTIVE: Bone formation/remodeling-associated biomarkers, such as osteocalcin, amino pro-peptide of type 1 collagen (P1NP) and CrossLaps (CTX) have been deregulated in type 2 diabetes mellitus (T2DM) patients. In particular, the T2DM-associated sclerostin markedly inhibits the bone formation, suppresses the osteoblast activity and downregulates the bone turnover. PATIENTS AND METHODS: In the present study, we examined the serum levels of sclerostin, osteocalcin, P1NP and CTX in the T2DM patients...
February 2017: European Review for Medical and Pharmacological Sciences
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