Abstract:
:Genome-wide association studies (GWAS) have demonstrated that genetic variation at the MADS box transcription enhancer factor 2, polypeptide C (MEF2C) locus is robustly associated with bone mineral density, primarily at the femoral neck. MEF2C is a transcription factor known to operate via the Wnt signaling pathway. Our hypothesis was that MEF2C regulates the expression of a set of molecular pathways critical to skeletal function. Drawing on our laboratory and bioinformatic experience with ChIP-seq, we analyzed ChIP-seq data for MEF2C available via the ENCODE project to gain insight in to its global genomic binding pattern. We aligned the ChIP-seq data generated for GM12878 (an established lymphoblastoid cell line) and, using the analysis package HOMER, a total of 17,611 binding sites corresponding to 8,118 known genes were observed. We then performed a pathway analysis of the gene list using Ingenuity. At 5 kb, the gene list yielded 'EIF2 Signaling' as the most significant annotation, with a P value of 5.01 × 10(-26). Moving further out, this category remained the top pathway at 50 and 100 kb, then dropped to just second place at 500 kb and beyond by 'Molecular Mechanisms of Cancer'. In addition, at 50 kb and beyond 'RANK Signaling in Osteoclasts' was a consistent feature and resonates with the main general finding from GWAS of bone density. We also observed that MEF2C binding sites were significantly enriched primarily near inflammation associated genes identified from GWAS; indeed, a similar enrichment for inflammation genes has been reported previously using a similar approach for the vitamin D receptor, an established key regulator of bone turnover. Our analyses point to known connective tissue and skeletal processes but also provide novel insights in to networks involved in skeletal regulation. The fact that a specific GWAS category is enriched points to a possible role of inflammation through which it impacts bone mineral density.
journal_name
Calcif Tissue Intjournal_title
Calcified tissue internationalauthors
Johnson ME,Deliard S,Zhu F,Xia Q,Wells AD,Hankenson KD,Grant SFdoi
10.1007/s00223-013-9824-5subject
Has Abstractpub_date
2014-04-01 00:00:00pages
396-402issue
4eissn
0171-967Xissn
1432-0827journal_volume
94pub_type
杂志文章abstract::Men and women (n = 518) receiving moderate-to-high doses of corticosteroids were enrolled in two studies with similar protocols and randomly assigned to receive either placebo or risedronate (2.5 or 5 mg) for 1 year. All patients received daily calcium supplementation (500-1000 mg), and most also received supplemental...
journal_title:Calcified tissue international
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1007/s002230001146
更新日期:2000-10-01 00:00:00
abstract::The Sarcopenia and Quality of Life questionnaire (SarQol®) is a self-administered multidimensional sarcopenia-specific tool designed for community-dwelling subjects aged 65 years and older. The purpose of the present study was to evaluate the psychometric properties of the Spanish version of the SarQoL®. A total of 25...
journal_title:Calcified tissue international
pub_type: 杂志文章
doi:10.1007/s00223-019-00635-9
更新日期:2020-03-01 00:00:00
abstract::Lumbar spine bone mass and density were measured with Dual photon absorptiometry (DPA) in 60 patients with crush fractures and 60 age-matched normal women. Short-term reproducibility of bone mineral density (BMD) was 1.3% in normal women and 2.5% in osteoporotic women; long-term reproducibility in normal women was 2.2...
journal_title:Calcified tissue international
pub_type: 杂志文章
doi:10.1007/BF02553274
更新日期:1988-12-01 00:00:00
abstract::Paget's disease of bone (PDB) is a chronic and focal bone disorder, characterized by increased osteoclast-mediated bone resorption and a subsequent compensatory increase in bone formation, resulting in a disorganized mosaic of woven and lamellar bone at one or more affected skeletal sites. As a result, bone pain, noti...
journal_title:Calcified tissue international
pub_type: 杂志文章,评审
doi:10.1007/s00223-019-00522-3
更新日期:2019-05-01 00:00:00
abstract::The goals of internal fixation are an accurate reduction and stable fixation in the presence of adequate bony vascularity. This can be achieved by a variety of means including plate fixation. A certain amount of periosteal stripping is necessary for proper open reduction of a fracture and for proper plate application....
journal_title:Calcified tissue international
pub_type: 杂志文章
doi:10.1007/s002239900080
更新日期:1996-07-01 00:00:00
abstract::Osteoarthritis and sarcopenia are the most frequently described musculoskeletal disorders in older persons but the intertwining of these conditions and of their functional and cellular causes is complex. This narrative review aims to identify the links between osteoarthritis and sarcopenia described 1-in clinical stud...
journal_title:Calcified tissue international
pub_type: 杂志文章,评审
doi:10.1007/s00223-020-00703-5
更新日期:2020-09-01 00:00:00
abstract::A case-control study was undertaken to understand the etiopathology of the bone deformities among young children in a fluoride-affected village of the Bihar State. Two villages were selected: one village with high fluoride in drinking water (7.9 +/- 4.15 ppm), and the other village with normal levels of fluoride (0.6 ...
journal_title:Calcified tissue international
pub_type: 杂志文章
doi:10.1007/s00223-005-0233-2
更新日期:2005-06-01 00:00:00
abstract::ATP is as effective as inorganic pyrophosphate in retarding the rate of dissolution of calcium hydroxyapatite at pH 7, ADP is less effective, and AMP is without effect. The inhibition is due to the adsorption of ATP and ADP units on the crystal surface. ...
journal_title:Calcified tissue international
pub_type: 杂志文章
doi:10.1007/BF02405386
更新日期:1984-12-01 00:00:00
abstract::In adult human bone, fluoride uptake is accompanied by an increase in apatite crystal size. This increase, however, is not isotropic but is restricted primarily to growth in width and/or thickness, with no measurable change in length. In the present study, seeded growth experiments were conducted in vitro to determine...
journal_title:Calcified tissue international
pub_type: 杂志文章
doi:10.1007/s002239900522
更新日期:1998-09-01 00:00:00
abstract::Racial differences in bone mineral density (BMD) appear to account in part for racial differences in the incidence of osteoporosis and fractures. We previously reported that the greater BMD in adult blacks compared with whites is associated with a higher serum 17 beta-estradiol and greater secretion of growth hormone ...
journal_title:Calcified tissue international
pub_type: 杂志文章
doi:10.1007/s00223-001-1068-0
更新日期:2002-03-01 00:00:00
abstract::The aim of this work was a preliminary assessment of the feasibility of using in vivo measurements of mechanical properties of bones to detect mineral loss and further to relate them to the tendency of the bone to fracture in the case of loss of minerals, such as in osteoporosis. Previous studies of bone strength in v...
journal_title:Calcified tissue international
pub_type: 杂志文章
doi:10.1007/BF00298727
更新日期:1993-03-01 00:00:00
abstract::Measurement of areal bone mineral density (aBMD) in intravertebral subregions may increase the diagnostic sensitivity of dual-energy X-ray absorptiometry (DXA)-derived parameters for vertebral fragility. This study investigated whether DXA-derived bone parameters in vertebral subregions were better predictors of verte...
journal_title:Calcified tissue international
pub_type: 杂志文章
doi:10.1007/s00223-014-9866-3
更新日期:2014-08-01 00:00:00
abstract::Dickkopf-1 (DKK1) and sclerostin are antagonists of the Wnt/β-catenin pathway and decreased expression of either results in increased bone formation and mass. As both affect the same signaling pathway, we aimed to elucidate the redundancy and/or compensation of sclerostin and DKK1. Weekly sclerostin antibody (Scl-Ab) ...
journal_title:Calcified tissue international
pub_type: 杂志文章
doi:10.1007/s00223-018-0420-6
更新日期:2018-09-01 00:00:00
abstract::Bone loss occurs as early as the third decade and its cumulative effect throughout adulthood may impact risk for osteoporosis in later life, however, the genes and environmental factors influencing early bone loss are largely unknown. We investigated the role of genes in the change in bone mineral density (BMD) in par...
journal_title:Calcified tissue international
pub_type: 杂志文章
doi:10.1007/s00223-008-9197-3
更新日期:2009-02-01 00:00:00
abstract::Osteoporosis is a common disease among patients undergoing transplantation. Its prevalence and complications have been well described in solid organ recipients, especially kidney, liver, and heart. However, studies in bone marrow transplantation (BMT) are scarce. Among the mechanisms invoked in the pathogenesis of BMT...
journal_title:Calcified tissue international
pub_type: 杂志文章
doi:10.1007/s002239900240
更新日期:1997-04-01 00:00:00
abstract::Cortical bone can be modeled as a complex hierarchical composite interrelating both structure and material properties on four levels of structural organization: molecular, ultrastructural, microscopic, and macroscopic. In young animals, the microstructural systems are long parallel lamellar units, plexiform bone, whic...
journal_title:Calcified tissue international
pub_type: 杂志文章
doi:10.1007/BF02406131
更新日期:1984-01-01 00:00:00
abstract::We have recently reported that soy isoflavones particularly when provided in the context of soy protein are capable of preventing loss of bone mineral density due to orchidectomy in F344 rats. We hypothesize, that soy isoflavones also exert beneficial effects on bone microstructural properties, in part, by enhancing b...
journal_title:Calcified tissue international
pub_type: 杂志文章
doi:10.1007/s00223-005-0069-9
更新日期:2006-06-01 00:00:00
abstract::Yerba mate (Ilex paraguariensis) is a xanthine-containing beverage, which is also rich in caffeine. Because caffeine has a negative impact on bone mineral density (BMD) mainly associated with low calcium (Ca) diets, there would be expected a negative effect of yerba mate on bone. In this study, Sprague-Dawley rats wer...
journal_title:Calcified tissue international
pub_type: 杂志文章
doi:10.1007/s00223-015-0043-0
更新日期:2015-11-01 00:00:00
abstract::We have previously shown that cyclosporin A (CsA) produces high bone remodeling with resorption exceeding formation and loss of bone volume in the rat. This may have important clinical implications where CsA is widely used in organ transplantation. 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) is a bone mineralizing hormone ...
journal_title:Calcified tissue international
pub_type: 杂志文章
doi:10.1007/BF02555980
更新日期:1990-09-01 00:00:00
abstract::The binding of prostaglandin E2 (PGE2) to bone cells was studied to provide direct evidence for the existence of specific receptors in bone. Bone cells were isolated by collagenase digestion of fetal and newborn rat calvaria. Isolated cells were incubated with 3H-PGE2 and collected on Millipore filters. Specific bindi...
journal_title:Calcified tissue international
pub_type: 杂志文章
doi:10.1007/BF02405038
更新日期:1983-01-01 00:00:00
abstract::Discarded tissues, like human amniotic membranes and adipose tissue, were investigated for the application of Decellularized Human Amniotic Membrane (DAM) as a viable scaffold for transplantation of Adipose-derived stromal cells (ASCs) in bone regeneration of non-healing calvarial defects in rats. Amniotic membrane wa...
journal_title:Calcified tissue international
pub_type: 杂志文章
doi:10.1007/s00223-020-00793-1
更新日期:2021-01-09 00:00:00
abstract::Ipriflavone (i.p.) positively affects bone density in postmenopausal osteoporosis, primarily by inhibiting bone resorption. Using in vitro models of human osteoblast differentiation, we have observed that i.p. and some of its metabolites stimulate the expression of bone sialoprotein, decorin, and type I collagen, and ...
journal_title:Calcified tissue international
pub_type: 杂志文章,评审
doi:10.1007/s002239900378
更新日期:1997-01-01 00:00:00
abstract::To determine the relationships among nutrients intake, bone mass, and bone turnover in women we have investigated these issues in a population-based, cross-sectional, observational study in one county in central Sweden. A total of 175 women aged 28-74 at entry to the study were included. Dietary assessment was made by...
journal_title:Calcified tissue international
pub_type: 杂志文章
doi:10.1007/BF00298425
更新日期:1995-08-01 00:00:00
abstract::We describe here the activity of a novel selective estrogen receptor modulator, SP500263. When given to adult ovariectomized (OVX) rats for 28 days at doses of 0.3, 1, or 3 mg/kg/day, we found that SP500263 partially protected against OVX-induced loss of bone mineral content in the distal ends of femurs and in the who...
journal_title:Calcified tissue international
pub_type: 杂志文章
doi:10.1007/s00223-002-1029-2
更新日期:2003-06-01 00:00:00
abstract::GNAS is one of the most complex gene loci in the human genome and encodes multiple gene products including Gsα, XLαs, NESP55, A/B, and AS transcripts. XLαs, the extra-large G protein ɑ-subunit, is paternally expressed. XLɑs and Gsɑ share the common 2-13 exons with different promoters and first exons. Therefore, XLɑs c...
journal_title:Calcified tissue international
pub_type: 杂志文章,评审
doi:10.1007/s00223-020-00714-2
更新日期:2020-09-01 00:00:00
abstract::In the rat, prolonged administration of the luteinizing, hormone-releasing hormone agonist buserelin (25 micrograms/kg body wt/day s.c.) lowers blood estradiol, raises bone resorption, and induces osteopenia. The present study was undertaken to determine whether withdrawal of buserelin normalizes blood estradiol, slow...
journal_title:Calcified tissue international
pub_type: 杂志文章
doi:10.1007/BF02555819
更新日期:1990-01-01 00:00:00
abstract::Until 2006 the only mutations known to cause osteogenesis imperfecta (OI) were in the two genes coding for type I collagen chains. These dominant mutations affecting the expression or primary sequence of collagen α1(I) and α2(I) chains account for over 90% of OI cases. Since then a growing list of mutant genes causing...
journal_title:Calcified tissue international
pub_type: 杂志文章,评审
doi:10.1007/s00223-013-9723-9
更新日期:2013-10-01 00:00:00
abstract::The feasibility of two noninvasive methods [dual photon absorptiometry (DPA) and dual energy X-ray absorptiometry (DXA)] for prediction in vivo of local variations of trabecular bone strength within the proximal tibia was evaluated in 14 cadaveric knees. Trabecular bone strength was measured using an osteopenetrometer...
journal_title:Calcified tissue international
pub_type: 杂志文章
doi:10.1007/s002239900131
更新日期:1996-10-01 00:00:00
abstract::The bone anabolic effect of parathyroid hormone (PTH) therapy is blunted when used in patients who were previously on bisphosphonate treatment. Osteocytes may play a role in the bisphosphonate silencing effect on PTH therapy since bisphosphonates have been shown to reach the lacunocanalicular system. In vivo osteocyte...
journal_title:Calcified tissue international
pub_type: 杂志文章
doi:10.1007/s00223-013-9720-z
更新日期:2013-06-01 00:00:00
abstract::The ability of 1,25(OH)2D3 and of 24,25(OH)2D3 to prevent or to heal rickets in chicks was evaluated by studies of plasma biochemistry, growth plate histology, bone morphometry and microradiography, and bone mineralization. 1,25(OH)2D3 at a dose of 100 ng/day produced fewest abnormalities compared with vitamin D3-trea...
journal_title:Calcified tissue international
pub_type: 杂志文章
doi:10.1007/BF02405303
更新日期:1984-01-01 00:00:00