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https://www.readbyqxmd.com/read/29792935/lp533401-restores-bone-health-in-5-6-nephrectomized-rats-by-a-decrease-of-gut-derived-serotonin-and-regulation-of-serum-phosphate-through-the-inhibition-of-phosphate-co-transporters-expression-in-the-kidneys
#1
Dariusz Pawlak, Beata Znorko, Bartlomiej Kalaska, Tomasz Domaniewski, Radosław Zawadzki, Paweł Lipowicz, Michał Doroszko, Urszula Łebkowska, Piotr Grabowski, Krystyna Pawlak
LP533401 is an orally bioavailable small molecule that inhibits tryptophan hydroxylase-1, an enzyme responsible for the synthesis of gut-derived serotonin (GDS). Recently, we showed that increased GDS in rats with chronic kidney disease (CKD) affected bone strength and metabolism. We tested the hypothesis that treatment with LP533401 could reverse CKD-induced bone loss in uremia. Sixteen weeks after 5/6 nephrectomy, rats were randomized into untreated (CKD), treated with vehicle (VEH) and LP533401 at a dose of 30 or 100 mg/kg daily for 8 weeks...
May 21, 2018: Bone
https://www.readbyqxmd.com/read/29787832/a-comparative-study-of-quality-of-life-functional-and-bone-outcomes-in-osteogenesis-imperfecta-with-bisphosphonate-therapy-initiated-in-childhood-or-adulthood
#2
Andrew G Feehan, Margaret R Zacharin, Angelina S Lim, Peter J Simm
Bisphosphonates have been used for treatment of bone fragility disorders for over 25 years to increase bone mineral density (BMD). Anecdotally, bisphosphonate-treated Osteogenesis Imperfecta (OI) has a different trajectory to the natural history of untreated OI in terms of fracture incidence, quality of life and physical function, with minimal published evidence to support this clinical observation. This study describes functional outcomes of a cohort of adults with OI, stratified according to severity and treated with intravenous bisphosphonates as children...
May 19, 2018: Bone
https://www.readbyqxmd.com/read/29782940/defining-osteoblast-and-adipocyte-lineages-in-the-bone-marrow
#3
J L Pierce, D L Begun, J J Westendorf, M E McGee-Lawrence
Bone is a complex endocrine organ that facilitates structural support, protection to vital organs, sites for hematopoiesis, and calcium homeostasis. The bone marrow microenvironment is a heterogeneous niche consisting of multipotent musculoskeletal and hematopoietic progenitors and their derivative terminal cell types. Amongst these progenitors, bone marrow mesenchymal stem/stromal cells (BMSCs) may differentiate into osteogenic, adipogenic, myogenic, and chondrogenic lineages to support musculoskeletal development as well as tissue homeostasis, regeneration and repair during adulthood...
May 18, 2018: Bone
https://www.readbyqxmd.com/read/29782939/global-deletion-of-tetraspanin-cd82-attenuates-bone-growth-and-enhances-bone-marrow-adipogenesis
#4
Alexis Bergsma, Sourik S Ganguly, Daniel Dick, Bart O Williams, Cindy K Miranti
CD82 is a widely expressed member of the tetraspanin family of transmembrane proteins known to control cell signaling, adhesion, and migration. Tetraspanin CD82 is induced over 9-fold during osteoclast differentiation in vitro; however, its role in bone homeostasis is unknown. A globally deleted CD82 mouse model was used to assess the bone phenotype. Based on microCT and 4-point bending tests, CD82-deficient bones are smaller in diameter and weaker, but display no changes in bone density. Histomorphometry shows a decrease in size, erosion perimeter, and number of osteoclasts in situ, with a corresponding increase in trabecular surface area, specifically in male mice...
May 18, 2018: Bone
https://www.readbyqxmd.com/read/29778716/the-hematopoietic-stem-cell-niche-what-s-so-special-about-bone
#5
REVIEW
Benjamin J Frisch
Hematopoietic stem cells (HSCs) require a supportive microenvironment to regulate their function and produce sufficient hematopoietic cells over the lifetime of an individual. With the exception of fish, all vertebrates, including mammals, maintain HSCs in a complex niche within the bone marrow. Several bone specific cellular populations have been implicated as components of the HSC niche and are part of a complex network that regulates HSC functions. However, the full extent of interactions within the HSC niche, and the role of individual cell populations remain to be fully elucidated...
May 17, 2018: Bone
https://www.readbyqxmd.com/read/29777919/brain-to-bone-what-is-the-contribution-of-the-brain-to-skeletal-homeostasis
#6
REVIEW
Anna Idelevich, Roland Baron
The brain, which governs most, if not all, physiological functions in the body, from the complexities of cognition, learning and memory, to the regulation of basal body temperature, heart rate and breathing, has long been known to affect skeletal health. In particular, the hypothalamus - located at the base of the brain in close proximity to the medial eminence, where the blood-brain-barrier is not as tight as in other regions of the brain but rather "leaky", due to fenestrated capillaries - is exposed to a variety of circulating body cues, such as nutrients (glucose, fatty acids, amino acids), and hormones (insulin, glucagon, leptin, adiponectin) [1-3]...
May 16, 2018: Bone
https://www.readbyqxmd.com/read/29777918/sex-differences-in-the-spatial-distribution-of-bone-in-relation-to-incident-hip-fracture-findings-from-the-ages-reykjavik-study
#7
Elisa A Marques, Julio Carballido-Gamio, Vilmundur Gudnason, Gunnar Sigurdsson, Sigurdur Sigurdsson, Thor Aspelund, Kristin Siggeirsdottir, Lenore Launer, Gudny Eiriksdottir, Thomas Lang, Tamara B Harris
In this case-cohort study, we used data-driven computational anatomy approaches to assess within and between sex spatial differences in proximal femoral bone characteristics in relation to incident hip fracture. One hundred male and 234 female incident hip fracture cases, and 1047 randomly selected noncase subcohort participants (562 female) were chosen from the population-based AGES-Reykjavik study (mean age of 77 years). The baseline -i.e. before hip fracture- hip quantitative computed tomography scans of these subjects were analyzed using voxel-based morphometry, tensor-based morphometry, and surface-based statistical parametric mapping to assess the spatial distribution of volumetric bone mineral density (vBMD), internal structure, and cortical bone properties (thickness, vBMD and trabecular vBMD adjacent to the endosteal surface) of the proximal femur, respectively, in relation to incident hip fracture...
May 16, 2018: Bone
https://www.readbyqxmd.com/read/29775762/aortic-vascular-calcification-is-inversely-associated-with-the-trabecular-bone-score-in-patients-receiving-dialysis
#8
Jasna Aleksova, Samantha Kurniawan, Mirna Vucak-Dzumhur, Peter Kerr, Peter R Ebeling, Frances Milat, Grahame J Elder
INTRODUCTION: Progressive chronic kidney disease (CKD) confers a marked increase in risk for vascular calcification, cardiovascular disease, fracture and mortality, with likely contributing factors including dysregulated bone metabolism and mineral homeostasis. In general population studies, increased vascular calcification is directly related to mortality and inversely related to bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA). In patients with CKD, abnormalities in turnover, mineralization and bone volume, reduce the ability of DXA to predict fracture...
May 15, 2018: Bone
https://www.readbyqxmd.com/read/29775761/the-bone-anabolic-effects-of-irisin-are-through-preferential-stimulation-of-aerobic-glycolysis
#9
Dingdong Zhang, ChuHyun Bae, Junghak Lee, Jiho Lee, Zeyu Jin, Myeongmo Kang, Young Suk Cho, Jeong-Han Kim, Weontae Lee, Sung-Kil Lim
Irisin, a recently identified hormone secreted by skeletal muscle in response to exercise, exhibits anabolic effects on the skeleton primarily through the stimulation of bone formation. However, the mechanism underlying the irisin-stimulated anabolic response remains largely unknown. To uncover the underlying mechanism, we biosynthesized recombinant irisin (r-irisin) using an Escherichia coli expression system and used it to treat several osteoblast cell types. Our synthesized r-irisin could promote proliferation and differentiation of osteoblasts as evidenced by enhanced expression of osteoblast-specific transcriptional factors, including Runt-related transcription factor-2 (Runx2), Oster (Osx), as well as early osteoblastic differentiation markers such as alkaline phosphatase (Alp) and collagen type I alpha 1 (Col1a1)...
May 15, 2018: Bone
https://www.readbyqxmd.com/read/29763751/integration-of-summary-data-from-gwas-and-eqtl-studies-identified-novel-causal-bmd-genes-with-functional-predictions
#10
Xiang-He Meng, Xiang-Ding Chen, Jonathan Greenbaum, Qin Zeng, Sheng-Lan You, Hong-Mei Xiao, Li-Jun Tan, Hong-Wen Deng
PURPOSE: Osteoporosis is a common global health problem characterized by low bone mineral density (BMD) and increased risk of fracture. Genome-wide association studies (GWAS) have identified >100 genetic loci associated with BMD. However, the functional genes responsible for most associations remain largely unknown. We conducted an innovative summary statistic data-based Mendelian randomization (SMR) analysis to identify novel causal genes associated with BMD and explored their potential functional significance...
May 12, 2018: Bone
https://www.readbyqxmd.com/read/29758362/the-anti-epileptic-drugs-valproate-carbamazepine-and-levetiracetam-cause-bone-loss-and-modulate-wnt-inhibitors-in-normal-and-ovariectomised-rats
#11
Bushra Parveen, Ambrish Kumar Tiwari, Moon Jain, Subhashis Pal, Naibedya Chattopadhyay, Manjari Tripathi, Divya Vohora
Secondary osteoporosis is the major concern associated with long term intake of antiepileptic drugs (AEDs). Women are the vulnerable targets owing to post-menopausal bone loss. In the present work, we evaluated the effect of 10 weeks of treatment with AED therapy (carbamazepine, CBZ, 75 mg/kg; sodium valproate, SVP, 300 mg/kg; levetiracetam, LTM, 150 mg/kg) on bone mineral density and microarchitecture at femoral epiphysis, lumbar vertebrae and proximal tibia of normal and ovariectomised Wistar rats...
May 11, 2018: Bone
https://www.readbyqxmd.com/read/29758361/bone-accrual-in-oligo-amenorrheic-athletes-eumenorrheic-athletes-and-non-athletes
#12
Vibha Singhal, Karen Campoverde Reyes, Brooke Pfister, Kathryn Ackerman, Meghan Slattery, Katherine Cooper, Alexander Toth, Nupur Gupta, Mark Goldstein, Kamryn Eddy, Madhusmita Misra
BACKGROUND: Mechanical loading improves bone mineral density (BMD) and strength while decreasing fracture risk. Cross-sectional studies show that exercise advantage is lost in oligo-amenorrheic athletes (OA). Longitudinal studies examining the opposing effects of exercise and hypogonadism on bone are lacking in adolescents/young adults. OBJECTIVE: Evaluate differences in bone accrual over 12 months in OA, eumenorrheic athletes (EA) and non-athletes (NA). We hypothesized that bone accrual would be lower in OA than EA and NA, with differences most pronounced at non-weight bearing trabecular sites...
May 11, 2018: Bone
https://www.readbyqxmd.com/read/29753718/early-tgf-%C3%AE-inhibition-in-mice-reduces-the-incidence-of-breast-cancer-induced-bone-disease-in-a-myeloid-dependent-manner
#13
Denise Buenrostro, Kristin A Kwakwa, Nicole E Putnam, Alyssa R Merkel, Joshua R Johnson, James E Cassat, Julie A Sterling
The tumor-cell microenvironment is recognized as a dynamic place where critical cell interactions occur and play an important role in altering tumorigenesis. While many studies have investigated the effects of cellular cross-talk within distinct tumor microenvironments, these interactions have yet to be fully examined in bone. It is well-established that many common cancers metastasize to bone, resulting in the development of tumor-induced bone disease (TIBD), a multi-facetted illness that is driven by complex cell interactions within the bone marrow...
May 10, 2018: Bone
https://www.readbyqxmd.com/read/29753717/trim38-regulates-nf-%C3%AE%C2%BAb-activation-through-tab2-degradation-in-osteoclast-and-osteoblast-differentiation
#14
Kabsun Kim, Jung Ha Kim, Inyoung Kim, Semun Seong, Nacksung Kim
The tripartite motif protein 38 (TRIM38), a member of the TRIM family, is involved in various cellular processes such as cell proliferation, differentiation, apoptosis, and antiviral defense. However, the role of TRIM38 in osteoclast and osteoblast differentiation is not yet known. In this study, we report the involvement of TRIM38 in osteoclast and osteoblast differentiation. Overexpression of TRIM38, in osteoclast precursor cells, attenuated receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclast formation, RANKL-triggered NF-κB activation, and expression of osteoclast marker genes, such as NFATc1, osteoclast-associated receptor (OSCAR), and tartrate-resistant acid phosphatase (TRAP); and down-regulation of TRIM38 expression showed the opposite effects...
May 10, 2018: Bone
https://www.readbyqxmd.com/read/29753150/identification-of-asymptomatic-frailty-vertebral-fractures-in-post-menopausal-women
#15
S Pizzato, C Trevisan, P Lucato, G Girotti, M Mazzochin, B M Zanforlini, G Bano, F Piovesan, A Bertocco, F Zoccarato, M Dianin, E Manzato, G Sergi
PURPOSE: Vertebral fractures are associated with persistent pain, disability and mortality. However, around two thirds of women with vertebral fractures are unaware of them. We aimed to analyze which factors could mostly be associated to the presence of vertebral fractures in post-menopausal women, and evaluate the effectiveness of current screening criteria for the detection of vertebral fractures in an outpatient setting. METHODS: We evaluated 1132 post-menopausal women referred to the osteoporosis outpatient clinic of the Geriatrics Department of Padova...
May 9, 2018: Bone
https://www.readbyqxmd.com/read/29751130/association-of-high-resolution-peripheral-quantitative-computed-tomography-hr-pqct-bone-microarchitectural-parameters-with-previous-clinical-fracture-in-older-men-the-osteoporotic-fractures-in-men-mros-study
#16
Howard A Fink, Lisa Langsetmo, Tien N Vo, Eric S Orwoll, John T Schousboe, Kristine E Ensrud
High-resolution peripheral quantitative computed tomography (HR-pQCT) assesses both volumetric bone mineral density (vBMD) and trabecular and cortical microarchitecture. However, studies of the association of HR-pQCT parameters with fracture history have been small, predominantly limited to postmenopausal women, often performed limited adjustment for potential confounders including for BMD, and infrequently assessed strength or failure measures. We used data from the Osteoporotic Fractures in Men (MrOS) study, a prospective cohort study of community-dwelling men aged ≥65 years, to evaluate the association of distal radius, proximal (diaphyseal) tibia and distal tibia HR-pQCT parameters measured at the Year 14 (Y14) study visit with prior clinical fracture...
May 8, 2018: Bone
https://www.readbyqxmd.com/read/29751129/selective-inhibition-of-src-family-kinases-by-su6656-increases-bone-mass-by-uncoupling-bone-formation-from-resorption-in-mice
#17
Cyril Thouverey, Serge Ferrari, Joseph Caverzasio
Mice deficient in the non-receptor tyrosine kinase Src exhibit high bone mass due to impaired bone resorption and increased bone formation. Although several Src family kinase inhibitors inhibit bone resorption in vivo, they display variable effects on bone formation. SU6656 is a selective Src family kinase inhibitor with weaker activity towards the non-receptor tyrosine kinase Abl and receptor tyrosine kinases which are required for appropriate osteoblast proliferation, differentiation and function. Therefore, we sought to determine whether SU6656 could increase bone mass by inhibiting bone resorption and by stimulating bone formation, and to explore its mechanisms of action...
May 8, 2018: Bone
https://www.readbyqxmd.com/read/29738854/age-related-changes-in-female-mouse-cortical-bone-microporosity
#18
Haniyeh Hemmatian, Michaël R Laurent, Astrid D Bakker, Dirk Vanderschueren, Jenneke Klein-Nulend, G Harry van Lenthe
Osteocyte lacunae are small cavities within the bone matrix. Their dimensions and spatial arrangement affect bone mechanical properties. Furthermore, their size and shape affect the strain in bone tissue close to the lacunae; hence, they are supposed to affect the mechanosensory function of the osteocytes residing in the lacunae. It was the purpose of this study to quantify the morphological features of osteocyte lacunae, whether these are affected by aging and whether these vary among different anatomical location...
May 5, 2018: Bone
https://www.readbyqxmd.com/read/29738853/osteocytic-perilacunar-canalicular-turnover-in-hemodialysis-patients-with-high-and-low-serum-pth-levels
#19
Aiji Yajima, Ken Tsuchiya, David B Burr, Daniel E Minner, Keith W Condon, Caroline A Miller, Shigeru Satoh, Masaaki Inaba, Takashi Nakayama, Tatsuhiko Tanizawa, Akemi Ito, Kosaku Nitta
Osteocytic perilacunar/canalicular turnover in hemodialysis patients has not yet been reported. Osteocyte lacunae in lamellar bone and woven bone were classified as eroded surface-, osteoid surface-, and quiescent surface-predominant osteocyte lacunae (ES-Lc, OS-Lc, QS-Lc, respectively) in 55 hemodialysis patients with either high- (n = 45) or low- (n = 10) parathyroid hormone levels, and 19 control subjects without chronic kidney disease. We calculated the area and number of ES-Lc, OS-Lc, and QS-Lc...
May 5, 2018: Bone
https://www.readbyqxmd.com/read/29730278/relationships-between-human-cortical-bone-toughness-and-collagen-cross-links-on-paired-anatomical-locations
#20
Rémy Gauthier, Hélène Follet, Max Langer, Evelyne Gineyts, Frédéric Rongiéras, Françoise Peyrin, David Mitton
Human cortical bone fracture processes depend on the internal porosity network down to the lacunar length scale. Recent results show that at the collagen scale, the maturation of collagen cross-links may have a negative influence on bone mechanical behavior. While the effect of pentosidine on human cortical bone toughness has been studied, the influence of mature and immature enzymatic cross-links has only been studied in relation to strength and work of fracture. Moreover, these relationships have not been studied on different paired anatomical locations...
May 3, 2018: Bone
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