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https://www.readbyqxmd.com/read/29208525/novel-familial-mutation-of-lrp5-causing-high-bone-mass-genetic-analysis-clinical-presentation-and-characterization-of-bone-matrix-mineralization
#1
K M Roetzer, G Uyanik, A Brehm, J Zwerina, S Zandieh, T Czech, P Roschger, B M Misof, K Klaushofer
The Wnt signalling pathway is a critical regulator of bone mass and quality. Several heterozygous mutations in the LRP5 gene, a Wnt co-receptor, causing high bone mass (LRP5-HBM) have been described to date. The pathogenic mechanism is thought to be a gain-of-function caused by impaired inhibition of the canonical Wnt signalling pathway, thereby leading to increased bone formation. We report the cases of two affected family members, a 53-year-old mother and her 23-year-old daughter, with high bone mass (T-scores mother: lumbar spine 11...
December 5, 2017: Bone
https://www.readbyqxmd.com/read/29208526/larg-gef-and-arhgap18-orchestrate-rhoa-activity-to-control-mesenchymal-stem-cell-lineage
#2
William R Thompson, Sherwin S Yen, Gunes Uzer, Zhihui Xie, Buer Sen, Maya Styner, Keith Burridge, Janet Rubin
The quantity and quality of bone depends on osteoblastic differentiation of mesenchymal stem cells (MSCs), where adipogenic commitment depletes the available pool for osteogenesis. Cell architecture influences lineage decisions, where interfering with cytoskeletal structure promotes adipogenesis. Mechanical strain suppresses MSC adipogenesis partially through RhoA driven enhancement of cytoskeletal structure. To understand the basis of force-driven RhoA activation, we considered critical GEFs (activators) and GAPs (inactivators) on bone marrow MSC lineage fate...
December 2, 2017: Bone
https://www.readbyqxmd.com/read/29198979/bone-volume-fraction-and-structural-parameters-for-estimation-of-mechanical-stiffness-and-failure-load-of-human-cancellous-bone-samples-in-vitro-comparison-of-ultrasound-transit-time-spectroscopy-and-x-ray-%C3%AE-ct
#3
Ali Hamed Alomari, Marie-Luise Wille, Christian M Langton
Conventional mechanical testing is the 'gold standard' for assessing the stiffness (N mm-1) and strength (MPa) of bone, although it is not applicable in-vivo since it is inherently invasive and destructive. The mechanical integrity of a bone is determined by its quantity and quality; being related primarily to bone density and structure respectively. Several non-destructive, non-invasive, in-vivo techniques have been developed and clinically implemented to estimate bone density, both areal (dual-energy X-ray absorptiometry (DXA)) and volumetric (quantitative computed tomography (QCT))...
November 30, 2017: Bone
https://www.readbyqxmd.com/read/29183783/mesenchymal-lineage-cells-and-their-importance-in-b-lymphocyte-niches
#4
REVIEW
Alanna C Green, Victoria Rudolph-Stringer, Andrew D Chantry, Joy Y Wu, Louise E Purton
Early B lymphopoiesis occurs in the bone marrow and is reliant on interactions with numerous cell types in the bone marrow microenvironment, particularly those of the mesenchymal lineage. Each cellular niche that supports the distinct stages of B lymphopoiesis is unique. Different cell types and signaling molecules are important for the progressive stages of B lymphocyte differentiation. Cells expressing CXCL12 and IL-7 have long been recognized as having essential roles in facilitating progression through stages of B lymphopoiesis...
November 26, 2017: Bone
https://www.readbyqxmd.com/read/29183785/ablation-of-gs%C3%AE-signaling-in-osteoclast-progenitor-cells-adversely-affects-skeletal-bone-maintenance
#5
REVIEW
Girish Ramaswamy, John Fong, Niambi Brewer, Hyunsoo Kim, Deyu Zhang, Yongwon Choi, Frederick S Kaplan, Eileen M Shore
Gsα, the alpha stimulatory subunit of heterotrimeric G proteins that activates downstream signaling through the adenylyl cyclase and cAMP/PKA pathway, plays an important role in bone development and remodeling. The role of Gsα in mesenchymal stem cell (MSC) differentiation to osteoblasts has been demonstrated in several mouse models of Gsα inactivation. Previously, using mice with heterozygous germline deletion of Gsα (Gnas+/p-), we identified a novel additional role for Gsα in bone remodeling, and showed the importance of Gnas in maintaining bone quality by regulating osteoclast differentiation and function...
November 25, 2017: Bone
https://www.readbyqxmd.com/read/29183784/osteocalcin-improves-insulin-resistance-and-inflammation-in-obese-mice-participation-of-white-adipose-tissue-and-bone
#6
REVIEW
J A C Guedes, J V Esteves, M R P T Morais, T M T Zorn, D T Furuya
AIMS/HYPOTHESIS: The discovery of osteocalcin, a protein synthetized by osteoblasts, as a hormone that has positive effects on insulin resistance, contributed to support the concept of bone as an endocrine organ. However, very little is known about the molecular pathways involved in osteocalcin improved-insulin resistance. The present study aimed to investigate the mechanisms of action of osteocalcin on insulin resistance and inflammation in obese mice and 3T3-L1 adipocytes. METHODS AND RESULTS: Lean control, saline-treated obese and uncarboxylated osteocalcin (uOC)-treated obese mice were subjected to insulin tolerance test in vivo...
November 25, 2017: Bone
https://www.readbyqxmd.com/read/29174564/crispr-cas9-engineered-osteogenesis-imperfecta-type-v-leads-to-severe-skeletal-deformities-and-perinatal-lethality-in-mice
#7
Frank Rauch, Yeqing Geng, Lisa Lamplugh, Bahareh Hekmatnejad, Marie-Hélène Gaumond, Janice Penney, Yojiro Yamanaka, Pierre Moffatt
Osteogenesis imperfecta (OI) type V is caused by an autosomal dominant mutation in the IFITM5 gene, also known as BRIL. The c.-14C>T mutation in the 5'UTR of BRIL creates a novel translational start site adding 5 residues (MALEP) in frame with the natural coding of BRIL. A neomorphic function has been proposed for the MALEP-BRIL but the mechanisms at play are still unknown. In order to further understand the effects of MALEP-BRIL in vivo, we generated a knockin (KI) mouse model having the exact genetic -14C>T replica of patients with OI type V...
November 22, 2017: Bone
https://www.readbyqxmd.com/read/29175272/fibrodysplasia-ossificans-progressiva-in-china
#8
REVIEW
Dunmin She, Keqin Zhang
Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare and devastating disorder characterized by cumulative episodes of progressive heterotopic ossification. It is estimated that there exist 600-700 patients in Mainland China. Nevertheless, due to the rarity, many FOP patients were initially misdiagnosed. Until now fewer than 150 patients have been identified in Mainland China. This review summarizes the epidemiology and clinical features of FOP patients, the progress of clinical and basic research in China, and the future of FOP care in China...
November 21, 2017: Bone
https://www.readbyqxmd.com/read/29175271/gnathodiaphyseal-dysplasia-severe-atypical-presentation-with-novel-heterozygous-mutation-of-the-anoctamin-gene-ano5
#9
Ghada A Otaify, Michael P Whyte, Gary S Gottesman, William H McAlister, J Eric Gordon, Abby Hollander, Marisa V Andrews, Samir K El-Mofty, Wei-Shen Chen, Deborah V Novack, Marina Stolina, Albert Woo, Panagiotis Katsonis, Olivier Lichtarge, Fan Zhang, Marwan Shinawi
Gnathodiaphyseal dysplasia (GDD; OMIM #166260) is an ultra-rare autosomal dominant disorder caused by heterozygous mutation in the anoctamin 5 (ANO5) gene and features fibro-osseous lesions of the jawbones, bone fragility with recurrent fractures, and bowing/sclerosis of tubular bones. The physiologic role of ANO5 is unknown. We report a 5-year-old boy with a seemingly atypical and especially severe presentation of GDD and unique ANO5 mutation. Severe osteopenia was associated with prenatal femoral fractures, recurrent postnatal fractures, and progressive bilateral enlargement of his maxilla and mandible beginning at ~2months-of-age that interfered with feeding and speech and required four debulking operations...
November 21, 2017: Bone
https://www.readbyqxmd.com/read/29175270/prevalence-of-pelvic-paget-s-disease-of-bone-in-france
#10
LETTER
B Mazières, J Coste, L Euller-Ziegler, P Fardellone, B Fautrel, J Pouchot, A-C Rat, C-H Roux, A Saraux, E Verrouil, F Guillemin
No abstract text is available yet for this article.
November 21, 2017: Bone
https://www.readbyqxmd.com/read/29175269/sclerostin-deficiency-modifies-the-development-of-ckd-mbd-in-mice
#11
Nadine Kaesler, Anja Verhulst, Annelies De Maré, Annika Deck, Geert J Behets, Ayshe Hyusein, Pieter Evenepoel, Jürgen Floege, Nikolaus Marx, Anne Babler, Ina Kramer, Michaela Kneissel, Rafael Kramann, Daniel Weis, Patrick C D'Haese, Vincent M Brandenburg
Sclerostin is a soluble antagonist of canonical Wnt signaling and a strong inhibitor of bone formation. We present experimental data on the role of sclerostin in chronic kidney disease - bone mineral disorder (CKD-MBD). METHODS: We performed 5/6 nephrectomies in 36-week-old sclerostin-deficient (SOST-/-) B6-mice and in C57BL/6J wildtype (WT) mice. Animals received a high phosphate diet for 11weeks. The bones were analyzed by high-resolution micro-computed tomography (μCT) and quantitative bone histomorphometry...
November 21, 2017: Bone
https://www.readbyqxmd.com/read/29170109/activin-a-amplifies-dysregulated-bmp-signaling-and-induces-chondro-osseous-differentiation-of-primary-connective-tissue-progenitor-cells-in-patients-with-fibrodysplasia-ossificans-progressiva-fop
#12
REVIEW
Haitao Wang, Eileen M Shore, Robert J Pignolo, Frederick S Kaplan
BACKGROUND: Fibrodysplasia ossificans progressiva (FOP), is caused by mutations in the type I BMP receptor ACVR1 that lead to increased activation of the BMP-pSmad1/5/8 signaling pathway. Recent findings suggest that Activin A (Act A) promiscuously stimulates the bone morphogenetic protein (BMP) signaling pathway in vitro and mediates heterotopic ossification (HO) in mouse models of FOP, but primary data from FOP patient cells are lacking. OBJECTIVE: To examine BMP-pSmad1/5/8 pathway signaling and chondro-osseous differentiation in response to endogenous and exogenous Act A in primary connective tissue progenitor cells [CTPCs; also known as stem cells from human exfoliated deciduous teeth (SHED) cells] from patients with FOP...
November 20, 2017: Bone
https://www.readbyqxmd.com/read/29170108/a-mathematical-multiscale-model-of-bone-remodeling-accounting-for-pore-space-specific-mechanosensation
#13
Maria-Ioana Pastrama, Stefan Scheiner, Peter Pivonka, Christian Hellmich
While bone tissue is a hierarchically organized material, mathematical formulations of bone remodeling are often defined on the level of a millimeter-sized representative volume element (RVE), "smeared" over all types of bone microstructures seen at lower observation scales. Thus, there is no explicit consideration of the fact that the biological cells and biochemical factors driving bone remodeling are actually located in differently sized pore spaces: active osteoblasts and osteoclasts can be found in the vascular pores, whereas the lacunar pores host osteocytes - bone cells originating from former osteoblasts which were then "buried" in newly deposited extracellular bone matrix...
November 20, 2017: Bone
https://www.readbyqxmd.com/read/29155245/answer-to-the-letter-to-the-editor-regarding-the-article-determinants-of-short-term-fracture-risk-in-patients-with-a-recent-history-of-low-trauma-non-vertebral-fracture
#14
LETTER
Aude Deloumeau, Anna Molto, Christian Roux, Karine Briot
No abstract text is available yet for this article.
November 16, 2017: Bone
https://www.readbyqxmd.com/read/29155244/letter-to-the-editor-determinants-of-short-term-fracture-risk-in-patients-with-a-recent-history-of-low-trauma-non-vertebral-fracture
#15
Hui-Jie Fan, Shu-Yin Liu, Zhi-Feng Sheng
No abstract text is available yet for this article.
November 16, 2017: Bone
https://www.readbyqxmd.com/read/29155243/the-24-25-to-25-hydroxyvitamin-d-ratio-and-fracture-risk-in-older-adults-the-cardiovascular-health-study
#16
Charles Ginsberg, Ronit Katz, Ian H de Boer, Bryan R Kestenbaum, Michel Chonchol, Michael G Shlipak, Mark J Sarnak, Andrew N Hoofnagle, Dena E Rifkin, Pranav S Garimella, Joachim H Ix
25-hydroxyvitamin D [25(OH)D] may not optimally indicate vitamin D receptor activity. Higher concentrations of its catabolic product 24,25-dihydroxyvitmin D [24,25(OH)2D] and a higher ratio of 24,25(OH)2D to 25(OH)D (the vitamin D metabolite ratio [VMR]) may provide additional information on receptor activity. We compared the strength of associations of these markers with serum PTH concentrations, hip bone mineral density (BMD), and risk of incident hip fracture in community-living older participants in the Cardiovascular Health Study...
November 16, 2017: Bone
https://www.readbyqxmd.com/read/29154969/adults-with-cystic-fibrosis-have-deficits-in-bone-structure-and-strength-at-the-distal-tibia-despite-similar-size-and-measuring-standard-and-relative-sites
#17
Kyle K Nishiyama, Sanchita Agarwal, Anna Kepley, Fernando Rosete, Yizhong Hu, X Edward Guo, Claire L Keating, Emily A DiMango, Elizabeth Shane
Individuals with cystic fibrosis (CF) have lower bone mineral density (BMD) by DXA and are at higher risk of fracture than healthy controls. However, the 2-dimensional measurement of areal BMD (aBMD) provided by DXA is influenced by bone size and the true extent of the bone deficit is unclear. Our objective was to use high-resolution peripheral quantitative computed tomography (HR-pQCT) and individual trabecula segmentation (ITS) analysis to compare volumetric BMD (vBMD), microarchitecture and estimated strength at the distal radius and tibia in 26 young adults with CF and 26 controls matched for age, gender, and race...
November 14, 2017: Bone
https://www.readbyqxmd.com/read/29154968/non-traumatic-osteonecrosis-of-the-femoral-head-is-associated-with-low-bone-mass
#18
Valérie Gangji, Muhammad S Soyfoo, Audrey Heuschling, Violaine Afzali, Rodrigo Moreno-Reyes, Joanne Rasschaert, Céline Gillet, Jean-Francois Fils, Jean-Philippe Hauzeur
OBJECTIVE: Osteoporosis (OP) and osteonecrosis of the femoral head (ONFH) share common clinical and pathophysiological features we sought to determine whether ONFH was associated with an increased prevalence of OP and whether the increased prevalence of OP was related to the stage of ONFH at diagnosis. METHODS: We included 243 patients with ONFH and 399 age and sex-matched healthy controls. Data was gathered including demography, risk factors, ARCO staging of ONFH and bone mineral density (BMD)...
November 14, 2017: Bone
https://www.readbyqxmd.com/read/29154967/bone-marrow-mechanotransduction-in-porcine-explants-alters-kinase-activation-and-enhances-trabecular-bone-formation-in-the-absence-of-osteocyte-signaling
#19
Kimberly J Curtis, Thomas R Coughlin, Devon E Mason, Joel D Boerckel, Glen L Niebur
Bone is a dynamic tissue that can adapt its architecture in response to mechanical signals under the control of osteocytes, which sense mechanical deformation of the mineralized bone. However, cells in the marrow are also mechanosensitive and may contribute to load-induced bone adaptation, as marrow is subjected to mechanical stress during bone deformation. We investigated the contribution of mechanotransduction in marrow cells to trabecular bone formation by applying low magnitude mechanical stimulation (LMMS) to porcine vertebral trabecular bone explants in an in situ bioreactor...
November 14, 2017: Bone
https://www.readbyqxmd.com/read/29081378/tnf%C3%AE-blockade-mediates-bone-protection-in-antigen-induced-arthritis-by-reducing-osteoclast-precursor-supply
#20
Stephanie Uster, Fernanda Matos Coelho, Daniel Aeberli, Jens V Stein, Wilhelm Hofstetter, Britta Engelhardt, Michael Seitz
Bone protective effects of TNFα inhibition in rheumatoid arthritis are thought to be mediated by inhibiting synovial osteoclast differentiation and activity. However, it has not been addressed, if TNFα inhibitors alter the pool of peripheral osteoclast precursor cells (OPCs). Here, we blocked TNFα function in C57BL/6 mice with antigen induced arthritis (AIA) using the soluble TNFα receptor etanercept. Synovial bone lesions and osteoclasts were markedly reduced upon Etanercept in the early chronic phase of AIA...
November 14, 2017: Bone
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