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Bone

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https://www.readbyqxmd.com/read/28434888/melorheostosis-exome-sequencing-of-an-associated-dermatosis-implicates-postzygotic-mosaicism-of-mutated-kras
#1
Michael P Whyte, Malachi Griffith, Lee Trani, Steven Mumm, Gary S Gottesman, William H McAlister, Kilannin Krysiak, Robert Lesurf, Zachary L Skidmore, Katie M Campbell, Ilana S Rosman, Susan Bayliss, Vinieth N Bijanki, Angela Nenninger, Brian A Van Tine, Obi L Griffith, Elaine R Mardis
Melorheostosis (MEL) is the rare sporadic dysostosis characterized by monostotic or polyostotic osteosclerosis and hyperostosis often distributed in a sclerotomal pattern. The prevailing hypothesis for MEL invokes postzygotic mosaicism. Sometimes scleroderma-like skin changes, considered a representation of the pathogenetic process of MEL, overlie the bony changes, and sometimes MEL becomes malignant. Osteopoikilosis (OPK) is the autosomal dominant skeletal dysplasia that features symmetrically distributed punctate osteosclerosis due to heterozygous loss-of-function mutation within LEMD3...
April 20, 2017: Bone
https://www.readbyqxmd.com/read/28433758/osteomicrobiology-the-influence-of-gut-microbiota-on-bone-in-health-and-disease
#2
Rheinallt M Jones, Jennifer G Mulle, Roberto Pacifici
No abstract text is available yet for this article.
April 19, 2017: Bone
https://www.readbyqxmd.com/read/28428078/kinetic-reconstruction-reveals-time-dependent-effects-of-romosozumab-on-bone-formation-and-osteoblast-function-in-vertebral-cancellous-and-cortical-bone-in-cynomolgus-monkeys
#3
Rogely Waite Boyce, Qing-Tian Niu, Michael S Ominsky
Romosozumab, a humanized monoclonal sclerostin antibody under development for the treatment of osteoporosis, has a unique mechanism of action on bone-increasing bone formation and decreasing bone resorption. The effects on bone formation are transient, eliciting a rapid increase in bone formation that attenuates with continued treatment. Although bone formation attenuates, bone mineral density (BMD) continues to increase. To explore potential tissue-level mechanisms that could contribute to a progressive increase in spine BMD, we used kinetic reconstruction techniques to examine the effects of romosozumab on modeling and remodeling units in vertebral cancellous bone from adult cynomolgus monkeys administered romosozumab for 10 and 28weeks...
April 18, 2017: Bone
https://www.readbyqxmd.com/read/28428079/mineralization-inhibiting-effects-of-transglutaminase-crosslinked-polymeric-osteopontin
#4
Betty Hoac, Valentin Nelea, Wenge Jiang, Mari T Kaartinen, Marc D McKee
Osteopontin (OPN) belongs to the SIBLING family (Small, Integrin-Binding LIgand N-linked Glycoproteins) of mineral-binding matrix proteins found in bones and teeth. OPN is a well-known inhibitor of matrix mineralization, and enzymatic modification of OPN can affect this inhibitory function. In bone, OPN exists both as a monomer and as a high-molecular-weight polymer - the latter is formed by transglutaminase-mediated crosslinking of glutamine and lysine residues in OPN to create homotypic protein assemblies...
April 17, 2017: Bone
https://www.readbyqxmd.com/read/28428077/molecular-bases-of-the-crosstalk-between-bone-and-muscle
#5
Gerard Karsenty, Paula Mera
Exercise is an evolutionary conserved survival function that nowadays has beneficial health effects. The increased metabolic activity of contracting skeletal muscle affects the biology of many organs involved in regulating muscle functions. The discovery of hormones and cytokines secreted by bone and skeletal muscle during exercise, has recently added experimental credence to the notion that a crosstalk exists between these organs. Bone through the hormone osteocalcin, promotes exercise capacity in the mouse...
April 17, 2017: Bone
https://www.readbyqxmd.com/read/28414141/temporal-role-of-macrophages-in-cancellous-bone-healing
#6
Olof Helge Sandberg, Love Tätting, Magnus Erik Bernhardsson, Per Aspenberg
Macrophages are important phagocytosing and cytokine producing cells with effects on fracture healing. We used clodronate-containing liposomes to reduce the number of macrophages, in order to study their role in the early phases of cancellous bone healing. Holes were drilled bilaterally into the cancellous bone of the proximal metaphysis of the tibia of 60 mice. A screw was inserted in the hole in the right tibia. The day of surgery was day 0. Clodronate-containing liposomes were injected intraperitoneally as a single injection either day -4 or -1 (before surgery) or day 1 or 3 (after surgery)...
April 14, 2017: Bone
https://www.readbyqxmd.com/read/28414140/shear-stress-inhibits-il-17a-mediated-induction-of-osteoclastogenesis-via-osteocyte-pathways
#7
Chongshan Liao, Tianfan Cheng, Shuai Wang, Chengfei Zhang, Lijian Jin, Yanqi Yang
Interleukin (IL)-17 is crucial to osteoclast differentiation and activation. Osteocytes support osteoclast formation and are thought to orchestrate bone remodeling in response to fluid flow. The contribution of IL-17 to osteocyte-related bone resorption remains unclear. Here, we used the osteocyte-like MLO-Y4 cell line to examine the role of IL-17 and fluid flow in osteoclastogenesis. It was the first time to demonstrate that IL-17A promoted MLO-Y4 cell proliferation, enhanced expression of receptor activator of nuclear factor κ-B ligand (RANKL) and tumor necrosis factor-α (TNF-α), and induced osteoclastogenesis when MLO-Y4 cells were co-cultured with bone marrow-derived macrophage (BMM) cells...
April 14, 2017: Bone
https://www.readbyqxmd.com/read/28412469/earliest-phases-of-chondrogenesis-are-dependent-upon-angiogenesis-during-ectopic-bone-formation-in-mice
#8
Beth Bragdon, Stephanie Lam, Sherif Aly, Alexandra Femia, Abigail Clark, Amira Hussein, Elise F Morgan, Louis C Gerstenfeld
Endochondral ossification is the process where cartilage forms prior to ossification and in which new bone forms during both fracture healing and ectopic bone formation. Transitioning to ossification is a highly coordinated process between hypertrophic chondrocytes, vascular endothelial cells, osteoblasts and osteoclasts. A critical biological process that is central to the interactions of these various cell types is angiogenesis. Although it is well established that angiogenesis is crucial for fracture repair, less is known pertaining to the role of angiogenesis in ectopic bone formation...
April 12, 2017: Bone
https://www.readbyqxmd.com/read/28411109/letter-to-the-editor-concerning-hajdu-cheney-syndrome-report-of-a-novel-notch2-mutation-and-treatment-with-denosumab-by-g-adami-et-al-bone-2016-92-150-156
#9
https://www.readbyqxmd.com/read/28412470/crosstalk-between-kidney-and-bone-bench-to-bedside
#10
EDITORIAL
Keith A Hruska, Beate Lanske, Orson W Moe
No abstract text is available yet for this article.
April 11, 2017: Bone
https://www.readbyqxmd.com/read/28411110/impaired-wnt-signaling-and-the-spine-heterozygous-wnt1-mutation-causes-severe-age-related-spinal-pathology
#11
Riikka E Mäkitie, Tuukka Niinimäki, Miika T Nieminen, Camilla Schalin-Jäntti, Jaakko Niinimäki, Outi Mäkitie
BACKGROUND: WNT signaling plays a major role in bone and cartilage metabolism. Impaired WNT/β-catenin signaling leads to early-onset osteoporosis, but specific features in bone and other tissues remain inadequately characterized. We have identified two large Finnish families with early-onset osteoporosis due to a heterozygous WNT1 mutation c.652T>G, p.C218G. This study evaluated the impact of impaired WNT/β-catenin signaling on spinal structures. METHODS: Altogether 18 WNT1 mutation-positive (age range 11-76years, median 49years) and 14 mutation-negative subjects (10-77years, median 43years) underwent magnetic resonance imaging (MRI) of the spine...
April 11, 2017: Bone
https://www.readbyqxmd.com/read/28390904/normal-bone-density-and-trabecular-bone-score-but-high-serum-sclerostin-in-congenital-generalized-lipodystrophy
#12
Josivan Gomes Lima, Lucia Helena C Nobrega, Natalia Nobrega Lima, Marcel Catão Ferreira Dos Santos, Maria de Fatima P Baracho, Renaud Winzenrieth, Francisco Bandeira, Carolina de O Mendes-Aguiar, Francisco Paulo Freire Neto, Leonardo Capistrano Ferreira, Clifford J Rosen, Selma Maria B Jeronimo
CONTEXT: Berardinelli-Seip Congenital Lipodystrophy (BSCL) is a rare autosomal recessive syndrome characterized by a difficulty in storing lipids in adipocytes, low body fat mass, hypoleptinemia, and hyperinsulinemia. Sclerostin is a product of SOST gene that blocks the Wnt/β-catenin pathway, decreasing bone formation and enhancing adipogenesis. There are no data about sclerostin in people with BSCL. OBJECTIVE: We aimed to evaluate serum sclerostin, bone mineral density (BMD), and L1-L4 Trabecular Bone Score (TBS) in BSCL patients, generating new knowledge about potential mechanisms involved in the bone alterations of these patients...
April 6, 2017: Bone
https://www.readbyqxmd.com/read/28373146/increased-detection-of-genetic-loci-associated-with-risk-predictors-of-osteoporotic-fracture-using-a-pleiotropic-cfdr-method
#13
Jonathan Greenbaum, Kehao Wu, Lan Zhang, Hui Shen, Jigang Zhang, Hong-Wen Deng
Although GWAS have been successful in identifying some osteoporosis associated loci, the findings explain only a small fraction of the total genetic variance. In this study we use a recently developed novel pleiotropic conditional false discovery rate (cFDR) method to identify novel genetic loci associated with two risk traits for osteoporotic fracture (the clinical outcome and end result of osteoporosis), Height (HT) and Femoral Neck (FNK) BMD. The cFDR method allows us to improve the detection of associated variants by incorporating any potentially shared genetic mechanisms between the two associated traits...
March 31, 2017: Bone
https://www.readbyqxmd.com/read/28366796/open-source-software-for-semi-automated-histomorphometry-of-bone-resorption-and-formation-parameters
#14
Rob J van 't Hof, Lorraine Rose, Euphemie Bassonga, Anna Daroszewska
Micro-CT analysis has become the standard method for assessing bone volume and architecture in small animals. However, micro-CT does not allow the assessment of bone turnover parameters such as bone formation rate and osteoclast (OC) number and surface. For these crucial variables histomorphometric analysis is still an essential technique. Histomorphometry however, is time consuming and, especially in mouse bones, OCs can be difficult to detect. The main purpose of this study was to develop and validate a relatively easy and rapid method to measure static and dynamic bone histomorphometry parameters...
March 31, 2017: Bone
https://www.readbyqxmd.com/read/28363808/validation-of-cortical-bone-mineral-density-distribution-using-micro-computed-tomography
#15
Maleeha Mashiatulla, Ryan D Ross, D Rick Sumner
Changes in the bone mineral density distribution (BMDD), due to disease or drugs, can alter whole bone mechanical properties such as strength, stiffness and toughness. The methods currently available for assessing BMDD are destructive and two-dimensional. Micro-computed tomography (μCT) has been used extensively to quantify the three-dimensional geometry of bone and to measure the mean degree of mineralization, commonly called the tissue mineral density (TMD). The TMD measurement has been validated to ash density; however parameters describing the frequency distribution of TMD have not yet been validated...
March 29, 2017: Bone
https://www.readbyqxmd.com/read/28347910/acute-lung-injury-complicating-acute-kidney-injury-a-model-of-endogenous-%C3%AE-klotho-deficiency-and-distant-organ-dysfunction
#16
REVIEW
Connie C W Hsia, Priya Ravikumar, Jianfeng Ye
The lung interfaces with atmospheric oxygen via a large surface area and is perfused by the entire venous return bearing waste products collected from the entire body. It is logical that the lung is endowed with generous anti-oxidative capacity derived both locally and from the circulation. The single-pass pleiotropic alpha-Klotho (αKlotho) protein was discovered when its genetic disruption led to premature multi-organ degeneration and early death. The extracellular domain of αKlotho is cleaved by secretases and released into circulation as endocrine soluble αKlotho protein and exerting wide-ranging cytoprotective effects including anti-oxidation on distant organs especially the lung, which exhibits high sensitivity to circulating αKlotho insufficiency...
March 24, 2017: Bone
https://www.readbyqxmd.com/read/28347909/bone-marrow-perfusion-measured-with-dynamic-contrast-enhanced-magnetic-resonance-imaging-is-correlated-to-body-mass-index-in-adults
#17
Jean-François Budzik, Guillaume Lefebvre, Hélène Behal, Sébastien Verclytte, Pierre Hardouin, Pedro Teixeira, Anne Cotten
Bone marrow metabolism is complex and far from being fully understood. Novel aspects, such as the roles of bone marrow adiposity and vascularisation in bone metabolism currently attract attention. There is also a growing interest in the influence obesity might have on bone metabolism. Our objective was to determine the effect of BMI on bone marrow perfusion parameters using dynamic contrast-enhanced magnetic resonance imaging. This prospective monocentric study was approved by our local Ethics committee. Written consent was obtained...
March 24, 2017: Bone
https://www.readbyqxmd.com/read/28341377/lrp5-from-bedside-to-bench-to-bone
#18
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/28336490/novel-therapeutic-interventions-for-pseudoachondroplasia
#19
Karen L Posey, Jacqueline T Hecht
Pseudoachondroplasia (PSACH), a severe short-limbed dwarfing condition, is associated with life-long joint pain and early onset osteoarthritis. PSACH is caused by mutations in cartilage oligomeric matrix protein (COMP), a pentameric matricellular protein expressed primarily in cartilage and other musculoskeletal tissues. Mutations in COMP diminish calcium binding and as a result perturb protein folding and export to the extracellular matrix. Mutant COMP is retained in the endoplasmic reticulum (ER) of growth plate chondrocytes resulting in massive intracellular COMP retention...
March 21, 2017: Bone
https://www.readbyqxmd.com/read/28323145/increased-cortical-porosity-is-associated-with-daily-not-weekly-administration-of-equivalent-doses-of-teriparatide
#20
Roger Zebaze, Ryoko Takao-Kawabata, Yu Peng, Ali Ghasem Zadeh, Kyoko Hirano, Hiroshi Yamane, Aya Takakura, Yukihiro Isogai, Toshinori Ishizuya, Ego Seeman
INTRODUCTION: The pharmacokinetic profile of parathyroid hormone (PTH) determines its effects on bone resorption and formation. When administered intermittently, anabolic effects are favored in comparison with the continuous treatment. Among the intermittent treatment regimens, lower frequency of administration may have a lower effect on bone remodeling. We therefore hypothesized that weekly administration of teriparatide will produce less increase in intracortical remodeling and porosity than reported using daily treatment...
March 18, 2017: Bone
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