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Vertebral Bone Remodeling

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https://www.readbyqxmd.com/read/29593116/tgf%C3%AE-facilitated-optic-fissure-fusion-and-the-role-of-bone-morphogenetic-protein-antagonism
#1
Max D Knickmeyer, Juan L Mateo, Priska Eckert, Eleni Roussa, Belal Rahhal, Aimee Zuniga, Kerstin Krieglstein, Joachim Wittbrodt, Stephan Heermann
The optic fissure is a transient gap in the developing vertebrate eye, which must be closed as development proceeds. A persisting optic fissure, coloboma, is a major cause for blindness in children. Although many genes have been linked to coloboma, the process of optic fissure fusion is still little appreciated, especially on a molecular level. We identified a coloboma in mice with a targeted inactivation of transforming growth factor β2 (TGFβ2). Notably, here the optic fissure margins must have touched, however failed to fuse...
March 2018: Open Biology
https://www.readbyqxmd.com/read/29559365/in-vivo-response-to-a-low-modulus-pmma-bone-cement-in-an-ovine-model
#2
Céline Robo, Gry Hulsart-Billström, Malin Nilsson, Cecilia Persson
Poly(methyl methacrylate) (PMMA) is the most commonly used material for the treatment of osteoporosis-induced vertebral compression fractures. However, its high stiffness may introduce an increased risk of adjacent vertebral fractures post-surgery. One alternative in overcoming this concern is the use of additives. This presents its own challenge in maintaining an adequate biocompatibility when modifying the base cement. The aim of this study was to evaluate the in vivo biocompatibility of linoleic acid (LA)-modified acrylic bone cement using a large animal model for the first time, in order to further advance towards clinical use...
March 17, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/29544018/low-dose-of-bisphosphonate-enhances-sclerostin-antibody-induced-trabecular-bone-mass-gains-in-brtl-osteogenesis-imperfecta-mouse-model
#3
Diana Olvera, Rachel Stolzenfeld, Joan C Marini, Michelle S Caird, Kenneth M Kozloff
Osteogenesis imperfecta (OI) is a genetic disorder characterized by altered bone quality and imbalanced bone remodeling, leading to skeletal fractures which are most prominent during childhood. Treatments for OI have focused on restoring pediatric bone density and architecture to recover functional strength and consequently reduce fragility. Though antiresorptive agents like bisphosphonates (BP) are currently the most common intervention for the treatment of OI, a number of studies have shown efficacy of sclerostin antibody (SclAb) in inducing gains in bone mass and reducing fragility in OI mouse models...
March 15, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/29522194/neutralization-of-cd40-ligand-costimulation-promotes-bone-formation-and-accretion-of-vertebral-bone-mass-in-mice
#4
Susanne Roser-Page, Tatyana Vikulina, Kanglun Yu, Meghan E McGee-Lawrence, M Neale Weitzmann
Objective: Immunosuppressive biologics are used in the management of RA and additional immunomodulators are under investigation including modulators of the CD40/CD40 ligand (CD40L) costimulation pathway. Tampering with immune function can have unanticipated skeletal consequences due to disruption of the immuno-skeletal interface, a nexus of shared cells and cytokine effectors serving discrete functions in both immune and skeletal systems. In this study, we examined the effect of MR1, a CD40L neutralizing antibody, on physiological bone remodelling in healthy mice...
March 7, 2018: Rheumatology
https://www.readbyqxmd.com/read/29417027/back-pain-an-unusual-manifestation-of-acute-lymphoblastic-leukemia-a-case-report-and-review-of-literature
#5
Magatha Sneha Latha, Ram Prakash Thirugnanasambandam, Padmasani Venkatraman, Julius Xavier Scott
Acute lymphoblastic leukemia (ALL) presented with bone pain and leukopenia is a well-recognized complex. Bone and joint pain are seen as presenting symptoms in 25% of patients with acute leukemia, but generalized osteopenia and vertebral complications are less common. Back pain due to vertebral changes as an early feature has been infrequently reported. We report a case of a 9-year-old female child who presented with back pain for 3 weeks. Blood counts and peripheral smear were normal. X-ray of the spine showed wedge-shaped deformity in L3-L5 vertebrae...
July 2017: Journal of Family Medicine and Primary Care
https://www.readbyqxmd.com/read/29363151/low-intensity-pulsed-ultrasound-accelerates-traumatic-vertebral-fracture-healing-by-coupling-proliferation-of-type-h-microvessels
#6
Suiyi Wu, Ximing Xu, Jingchuan Sun, Yao Zhang, Jiangang Shi, Tianming Xu
OBJECTIVES: Patients with traumatic vertebral fractures often have major associated postoperative morbidities such as healing failure and kyphosis. Low-intensity pulsed ultrasound (US) has been found to promote bone fracture healing. The objectives of our study were to determine whether low-intensity pulsed US could promote traumatic vertebral fracture healing and to explore its inner mechanisms. METHODS: A rat model of traumatic vertebral fracture was created and treated with low-intensity pulsed US after surgery...
January 24, 2018: Journal of Ultrasound in Medicine: Official Journal of the American Institute of Ultrasound in Medicine
https://www.readbyqxmd.com/read/29230102/specific-deletion-of-%C3%AE-catenin-in-col2-expressing-cells-leads-to-defects-in-epiphyseal-bone
#7
Tingyu Wang, Jun Li, Guang-Qian Zhou, Peter Ma, Yue Zhao, Baoli Wang, Di Chen
The role of canonical Wnt/β-catenin signaling in postnatal bone growth has not been fully defined. In the present studies, we generated β-catenin conditional knockout (KO) mice and deleted β-catenin in Col2 -expressing chondrocytes and mesenchymal progenitor cells. Findings from analyzing the β - cateninCol2CreER KO mice revealed severe bone destruction and bone loss phenotype in epiphyseal bone, probably due to the increase in osteoclast formation and the accumulation of adipocytes in this area. In addition, we also found bone destruction and bone loss phenotype in vertebral bone in β - cateninCol2CreER KO mice...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/29180199/dose-dependent-effect-of-parathyroid-hormone-on-fracture-healing-and-bone-formation-in-mice
#8
Alexander Milstrey, Britta Wieskoetter, Daniel Hinze, Niklas Grueneweller, Richard Stange, Thomas Pap, Michael Raschke, Patric Garcia
BACKGROUND: Parathyroid hormone (PTH) is the only clinically approved osteoanabolic drug for osteoporosis treatment. However, PTH is not established for the treatment of fracture healing, and doses of PTH diverge significantly between different studies. We hypothesized that the effect of PTH on promoting fracture healing and bone formation is dose dependent. MATERIALS AND METHODS: In vivo, mice were treated with PTH (10, 40, and 200 μg/kg) in a closed femoral fracture model...
December 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/29103161/multiple-vertebral-osteonecroses-k%C3%A3-mmell-s-disease-after-10%C3%A2-years-on-denosumab-is-osteocyte-apoptosis-to-blame
#9
Yves Maugars, Géraldine Bart, Pascale Guillot, Marguerite Chemel-Mary, Joëlle Glémarec, Mélanie Gahier-Penhoat, Benoit Le Goff, Christelle Darrieutort-Laffite
We report here a case of multiple vertebral osteonecroses with intrasomatic gaseous dissection (Kümmell's disease) occurring 1 year after the end of a 10-year course of denosumab treatment for osteoporosis without fractures. Histomorphometry and bone remodeling markers revealed major bone resorption and the persistence of an inhibition of bone formation. The presence of multiple empty lacunae in the bone provided evidence for high levels of osteocyte apoptosis. Osteocytes direct bone resorption (via the RANK/RANK-L/osteoprotegerin system) and formation (Wnt system, with SOST and DKK1) pathways...
November 4, 2017: Calcified Tissue International
https://www.readbyqxmd.com/read/29044725/serum-sclerostin-levels-in-adults-with-osteogenesis-imperfecta-comparison-with-normal-individuals-and-response-to-teriparatide-therapy
#10
Lindsey Nicol, Ying Wang, Rosamund Smith, John Sloan, Sandesh Cs Nagamani, Jay Shapiro, Brendan Lee, Eric Orwoll
Sclerostin (SOST), a glycoprotein primarily derived from osteocytes, is an important regulator of bone remodeling. Osteogenesis imperfecta (OI) is a heritable disorder of bone characterized by low bone mass, bone fragility, recurrent fractures, and bone deformities. Altered SOST-mediated signaling may have a role in pathogenesis of type I collagen-related OI; however, this has not been evaluated in humans. We measured serum SOST levels in adults with OI who were enrolled in a randomized, placebo-controlled clinical trial that evaluated the effects of osteoanabolic therapy with teriparatide...
February 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/29017495/treatment-of-thoracic-or-lumbar-burst-fractures-with-balloon-assisted-endplate-reduction-using-tricalcium-phosphate-cement-histological-and-radiological-evaluation
#11
Joep Kitzen, Martijn G M Schotanus, Herbert S W Plasschaert, Frans-Jan H Hulsmans, Pieter B J Tilman
BACKGROUND: Short-segment pedicle-screw instrumentation is frequently used to stabilize thoracolumbar burst fractures. A recognized disadvantage of this procedure is recurrent kyphosis from intervertebral disc creep into the fractured central endplate. Balloon Assisted Endplate Reduction (BAER) using Tricalcium Phosphate bone cement (TCP) enables elevation of the centrally depressed endplate. Our objective was to evaluate the bone-tissue response to TCP and to analyse whether BAER using TCP can prevent recurrent kyphosis after removal of the instrumentation...
October 10, 2017: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/28883093/role-of-the-ecm-in-notochord-formation-function-and-disease
#12
REVIEW
Valeria Trapani, Paolo Bonaldo, Diana Corallo
The notochord is a midline structure common to all chordate animals; it provides mechanical and signaling cues for the developing embryo. In vertebrates, the notochord plays key functions during embryogenesis, being a source of developmental signals that pattern the surrounding tissues. It is composed of a core of vacuolated cells surrounded by an epithelial-like sheath of cells that secrete a thick peri-notochordal basement membrane made of different extracellular matrix (ECM) proteins. The correct deposition and organization of the ECM is essential for proper notochord morphogenesis and function...
October 1, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28821457/spontaneous-mutation-of-dock7-results-in-lower-trabecular-bone-mass-and-impaired-periosteal-expansion-in-aged-female-misty-mice
#13
Phuong T Le, Kathleen A Bishop, David E Maridas, Katherine J Motyl, Daniel J Brooks, Kenichi Nagano, Roland Baron, Mary L Bouxsein, Clifford J Rosen
Misty mice (m/m) have a loss of function mutation in Dock7 gene, a guanine nucleotide exchange factor, resulting in low bone mineral density, uncoupled bone remodeling and reduced bone formation. Dock7 has been identified as a modulator of osteoblast number and in vitro osteogenic differentiation in calvarial osteoblast culture. In addition, m/m exhibit reduced preformed brown adipose tissue innervation and temperature as well as compensatory increase in beige adipocyte markers. While the low bone mineral density phenotype is in part due to higher sympathetic nervous system (SNS) drive in young mice, it is unclear what effect aging would have in mice homozygous for the mutation in the Dock7 gene...
December 2017: Bone
https://www.readbyqxmd.com/read/28796721/mechanisms-predisposing-factors-and-prognosis-of-intraoperative-vertebral-subluxation-during-pedicle-subtraction-osteotomy-in-surgical-correction-of-thoracolumbar-kyphosis-secondary-to-ankylosing-spondylitis
#14
Bang-Ping Qian, Sai-Hu Mao, Jun Jiang, Bin Wang, Yong Qiu
STUDY DESIGN: A retrospective study. OBJECTIVE: To analyze the mechanisms, predisposing factors, and prognosis of the intraoperative vertebral subluxation (VS) during pedicle subtraction osteotomy (PSO) for thoracolumbar kyphosis secondary to ankylosing spondylitis (AS). SUMMARY OF BACKGROUND DATA: VS is one of the most daunting challenges that surgeons encounter during PSO closure, especially in patients with AS with ankylosed and mostly osteoporotic spine...
August 15, 2017: Spine
https://www.readbyqxmd.com/read/28727345/-denosumab-in-clinical-practice-beware-before-during-and-after
#15
Olivier Lamy, Elena Gonzalez-Rodriguez, Delphine Stoll, Bérengère Aubry-Rozier
Denosumab is a very effective treatment of osteoporosis, easy to use and very well tolerated. Due to some associated risks, a close clinical follow-up is necessary. Before the first injection, it is necessary to correct hypocalcaemia or vitamin D deficiency when present. Calcemia has to be followed in case of renal insufficiency. Injections of denosumab should be done scrupulously every 6 months (± 3 weeks). Discontinuation of denosumab is associated with a severe rebound effect characterized by increased markers of bone remodeling, a rapid decrease of bone density values, and a risk of multiple spontaneous vertebral fractures...
April 19, 2017: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28631442/osteoblast-migration-in-vertebrate-bone
#16
Antonia Thiel, Marie K Reumann, Adele Boskey, Johannes Wischmann, Rüdiger von Eisenhart-Rothe, Philipp Mayer-Kuckuk
Bone formation, for example during bone remodelling or fracture repair, requires mature osteoblasts to deposit bone with remarkable spatial precision. As osteoblast precursors derive either from circulation or resident stem cell pools, they and their progeny are required to migrate within the three-dimensional bone space and to navigate to their destination, i.e. to the site of bone formation. An understanding of this process is emerging based on in vitro and in vivo studies of several vertebrate species. Receptors on the osteoblast surface mediate cell adhesion and polarization, which induces osteoblast migration...
February 2018: Biological Reviews of the Cambridge Philosophical Society
https://www.readbyqxmd.com/read/28591104/myeloma-bone-disease-pathogenesis-and-treatment
#17
REVIEW
Elizabeth K O'Donnell, Noopur S Raje
Bone involvement manifesting as osteolytic bone disease (OBD) or osteopenia is one of the defining features of multiple myeloma (MM). Osteolytic lesions develop in nearly 90% of patients with MM, and these are frequently complicated by skeleton-related events (SREs) such as severe bone pain, pathologic fractures, vertebral collapse, hypercalcemia, and spinal cord compression. SREs have a negative effect on patients' quality of life and affect their long-term outcomes, including survival. In MM, the delicate balance between bone formation and bone destruction is perturbed...
April 2017: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/28585249/closure-of-the-vertebral-canal-in-human-embryos-and-fetuses
#18
Hayelom K Mekonen, Jill P J M Hikspoors, Greet Mommen, Nutmethee Kruepunga, S Eleonore Köhler, Wouter H Lamers
The vertebral column is the paradigm of the metameric architecture of the vertebrate body. Because the number of somites is a convenient parameter to stage early human embryos, we explored whether the closure of the vertebral canal could be used similarly for staging embryos between 7 and 10 weeks of development. Human embryos (5-10 weeks of development) were visualized using Amira 3D(®) reconstruction and Cinema 4D(®) remodelling software. Vertebral bodies were identifiable as loose mesenchymal structures between the dense mesenchymal intervertebral discs up to 6 weeks and then differentiated into cartilaginous structures in the 7th week...
June 5, 2017: Journal of Anatomy
https://www.readbyqxmd.com/read/28458516/profile-of-romosozumab-and-its-potential-in-the-management-of-osteoporosis
#19
REVIEW
Sian Yik Lim, Marcy B Bolster
Increased understanding of bone biology has led to the discovery of several unique signaling pathways that regulate bone formation and resorption. The Wnt signaling pathway plays a significant role in skeletal development, adult skeletal homeostasis, and bone remodeling. Sclerostin is an inhibitor of the Wnt signaling pathway. Romosozumab, a humanized monoclonal antibody that binds to sclerostin, prevents sclerostin from exerting this inhibitory effect. Therefore, in the presence of romosozumab, the Wnt signaling pathway is activated leading to bone formation and bone mineral density gain...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28446689/bone-clarity-clearing-imaging-and-computational-analysis-of-osteoprogenitors-within-intact-bone-marrow
#20
Alon Greenbaum, Ken Y Chan, Tatyana Dobreva, David Brown, Deepak H Balani, Rogely Boyce, Henry M Kronenberg, Helen J McBride, Viviana Gradinaru
Bone tissue harbors unique and essential physiological processes, such as hematopoiesis, bone growth, and bone remodeling. To enable visualization of these processes at the cellular level in an intact environment, we developed "Bone CLARITY," a bone tissue clearing method. We used Bone CLARITY and a custom-built light-sheet fluorescence microscope to detect the endogenous fluorescence of Sox9-tdTomato(+) osteoprogenitor cells in the tibia, femur, and vertebral column of adult transgenic mice. To obtain a complete distribution map of these osteoprogenitor cells, we developed a computational pipeline that semiautomatically detects individual Sox9-tdTomato(+) cells in their native three-dimensional environment...
April 26, 2017: Science Translational Medicine
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