Abstract：
:Tight interactions among different cell types contributing to bone formation are of key importance in the maintenance of bone homeostasis. Based on the high similarity in responses to (anti)osteogenic signals between zebrafish scales and mammalian bone, we developed and validated a model to screen large numbers of compounds using ex-vivo cultured scales of a sp7:luciferase transgenic zebrafish. This model combines the high predictive value of explant cultures with quick, sensitive, and quantifiable readout converging the effects via various pathways including WNT-signaling, to SP7/osterix promoter activity. Sp7 is pivotal in osteoblast differentiation and activity and its promoter activity provides an excellent surrogate for sp7 expression. Bmp-2a was shown to dose-dependently increase sp7-driven luciferase activity ex vivo. Next, we identified novel effects on bone for 51.7% of the compounds from a small library of WNT-signaling modulators, including a strong osteogenic effect for niclosamide. From all previously characterized compounds, the effect on bone was correctly predicted for 70% of compounds, resulting in a 7% false positive- and 21% false negative rate. The proposed sp7:luciferase zebrafish scale model is unique, powerful and efficient new tool to assess compounds with osteogenic effects, prior to further testing in rodents.
journal_name
Bonejournal_title
Boneauthors
de Vrieze E,Zethof J,Schulte-Merker S,Flik G,Metz JRdoi
10.1016/j.bone.2015.01.006subject
Has Abstractpub_date
2015-05-01 00:00:00pages
106-13eissn
8756-3282issn
1873-2763pii
S8756-3282(15)00010-1journal_volume
74pub_type
杂志文章相关文献
BONE文献大全abstract：:Results in small patient series suggest that cyclical intravenous treatment with pamidronate can lead to reshaping of compressed vertebral bodies in children and adolescents with osteogenesis imperfecta (OI), but more detailed analyses are lacking. In this study of patients with moderate to severe OI (age range 0.1 to...
journal_title：Bone
pub_type： 杂志文章
doi：10.1016/j.bone.2006.04.004
更新日期：2006-10-01 00:00:00
abstract：:If muscle force is a primary source for triggering bone adaptation, with disuse and reloading, bone changes should follow muscle changes. We examined the timing and magnitude of changes in muscle cross-sectional area (MCSA) and bone architecture in response to muscle inactivity following botulinum toxin (BTX) injectio...
journal_title：Bone
pub_type： 杂志文章
doi：10.1016/j.bone.2009.10.016
更新日期：2010-01-01 00:00:00
abstract：:Osteoporosis is the consequence of altered bone metabolism resulting in the systemic reduction of bone strength and increased risk of fragility fractures. MicroRNAs (miRNAs) regulate gene expression on a post-transcriptional level and are known to take part in the control of bone formation and bone resorption. In addi...
journal_title：Bone
pub_type： 杂志文章
doi：10.1016/j.bone.2015.05.027
更新日期：2015-10-01 00:00:00
abstract：INTRODUCTION:High plasma homocysteine (Hcy) levels have been associated with increased risk of fracture. Since Hcy has been shown to induce apoptosis in many cell types, including vascular endothelial cells, we hypothesized that Hcy would have a similar apoptotic effect on osteoblasts, leading to osteoporosis by reduci...
journal_title：Bone
pub_type： 杂志文章
doi：10.1016/j.bone.2006.03.004
更新日期：2006-09-01 00:00:00
abstract：BACKGROUND:Several epidemiological studies have shown an association between bone mineral density (BMD) and risk of breast cancer in postmenopausal women, but it remains unknown whether bone turnover is associated with increased risk of cancer. The aim of this study was to investigate if markers of bone formation and r...
journal_title：Bone
pub_type： 杂志文章
doi：10.1016/j.bone.2019.05.032
更新日期：2019-10-01 00:00:00
abstract：:The R51Q mutation in sorting nexin 10 (SNX10) was shown to cause a lethal genetic disease in humans, namely autosomal recessive osteopetrosis (ARO). We describe here the first R51Q SNX10 knock-in mouse model and show that mice homozygous for this mutation exhibit massive, early-onset, and widespread osteopetrosis. The...
journal_title：Bone
pub_type： 杂志文章
doi：10.1016/j.bone.2020.115360
更新日期：2020-07-01 00:00:00
abstract：:Osteogenesis occurs in striking interaction with angiogenesis. There is growing evidence that endothelial cells are involved in the modulation of osteoblast differentiation. We hypothesized that primary human umbilical vein endothelial cells (HUVEC) should be able to modulate primary human osteoprogenitors (HOP) funct...
journal_title：Bone
pub_type： 杂志文章
doi：10.1016/j.bone.2008.01.025
更新日期：2008-06-01 00:00:00
abstract：:Heterotopic ossification (HO) involves formation of endochondral bone at non-skeletal sites, is prevalent in severely wounded service members, and causes significant complications and delayed rehabilitation. As common prophylactic treatments such as anti-inflammatory drugs and irradiation cannot be used after multi-sy...
journal_title：Bone
pub_type： 杂志文章
doi：10.1016/j.bone.2016.06.014
更新日期：2016-09-01 00:00:00
abstract：:Bone turnover occurs at discreet sites in the remodeling skeleton. The focal nature of this process indicates that local cues may facilitate the activation of bone cells by systemic factors. Nucleotides such as adenosine triphosphate (ATP) are locally released, short-lived, yet potent extracellular signaling molecules...
journal_title：Bone
pub_type： 杂志文章,评审
doi：10.1016/s8756-3282(01)00430-6
更新日期：2001-05-01 00:00:00
abstract：BACKGROUND:Cancer progression and metastasis occur such that cells with acquired mutations enhancing growth and survival (or inhibiting cell death) increase in number, a concept that has been recognized as analogous to Darwinian evolution of species since Peter C. Nowell's description in 1976. Selective forces include ...
journal_title：Bone
pub_type： 杂志文章
doi：10.1016/j.bone.2015.04.046
更新日期：2015-09-01 00:00:00
abstract：:The potential of whole body vibration (WBV) to maintain or enhance musculoskeletal strength during ageing is of increasing interest, with both low and high magnitude WBV having been shown to maintain or increase bone mineral density (BMD) at the lumbar spine and femoral neck. The aim of this study was to determine how...
journal_title：Bone
pub_type： 杂志文章
doi：10.1016/j.bone.2020.115802
更新日期：2021-03-01 00:00:00
abstract：INTRODUCTION:Teriparatide is a bone formation agent that increases bone turnover and mass, resulting in an increase in bone strength and a decrease in fracture risk. METHODS:The primary purpose of this analysis was to evaluate the association between pretreatment bone turnover marker (BTM) concentrations and the absol...
journal_title：Bone
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1016/j.bone.2006.02.003
更新日期：2006-08-01 00:00:00
abstract：:It is well known that physical inactivity leads to loss of muscle mass, but it also causes bone loss. Mechanistically, osteoclastogenesis and bone resorption have recently been shown to be regulated by vibration. However, the underlying mechanism behind the inhibition of osteoclast formation is yet unknown. Therefore,...
journal_title：Bone
pub_type： 杂志文章
doi：10.1016/j.bone.2013.08.020
更新日期：2013-12-01 00:00:00
abstract：:We investigated the bone remodeling activity on titanium implants with different surface roughnesses using a confocal laser scanning microscope (CLSM). Two kinds of implants were used, the machined smooth-surfaced titanium and the plasma-sprayed rough-surfaced titanium. These implants were randomly inserted in a rabbi...
journal_title：Bone
pub_type： 杂志文章
doi：10.1016/s8756-3282(97)00204-4
更新日期：1997-12-01 00:00:00
abstract：: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...
journal_title：Bone
pub_type： 杂志文章,评审
doi：10.1016/j.bone.2018.05.019
更新日期：2019-01-01 00:00:00
abstract：:One main problem associated with alveolar bone augmentation in implant dentistry is resorption of grafted bone, which may be further compromised by systemic skeletal disorders such as osteoporosis. Zoledronate acid (ZOL) is the most potent bisphosphonate to treat osteoporosis and therefore it is hypothesized to be abl...
journal_title：Bone
pub_type： 杂志文章
doi：10.1016/j.bone.2011.10.011
更新日期：2012-01-01 00:00:00
abstract：:Autologous marrow stromal cells have been proposed as an adjuvant in the treatment of bone defects and diseases. This will require the development of culture conditions that permit their rapid expansion ex vivo while retaining their potential for further differentiation. Fibroblast growth factor (FGF)-2 has been propo...
journal_title：Bone
pub_type： 杂志文章
doi：10.1016/s8756-3282(00)00319-7
更新日期：2000-08-01 00:00:00
abstract：:Bone morphogenetic proteins (BMPs) were first described over 50 years ago as potent inducers of ectopic bone formation when administrated subcutaneously. Preclinical studies have extensively examined the osteoinductive properties of BMPs in vitro and new bone formation in vivo. BMPs (BMP-2, BMP-7) have been used in or...
journal_title：Bone
pub_type： 杂志文章
doi：10.1016/j.bone.2020.115513
更新日期：2020-09-01 00:00:00
abstract：:We have previously shown that in osteoblasts Sox2 expression can be induced by Fgfs, and can inhibit Wnt signaling and differentiation. Furthermore, in mice in which Sox2 is conditionally deleted in the osteoblastic lineage, bones are osteopenic, and Sox2 inactivation in cultured osteoblasts leads to a loss of prolife...
journal_title：Bone
pub_type： 杂志文章
doi：10.1016/j.bone.2011.06.008
更新日期：2011-10-01 00:00:00
abstract：:As the world's population ages, the occurrence of osteoporosis-related fractures is projected to increase. Low areal bone mineral density (aBMD), a well-known risk factor for fractures, may be influenced by physical activity (PA). In this cross-sectional study, we aimed to investigate potential associations between ob...
journal_title：Bone
pub_type： 临床试验,杂志文章
doi：10.1016/j.bone.2015.07.001
更新日期：2015-12-01 00:00:00
abstract：:We investigated the effect of 2-beta-(3-hydroxypropoxy)-1alpha,25-dihydroxyvitamin D3 (ED-71) on the modeling of bone in distraction osteogenesis. The tibiae of 30 rabbits were lengthened by 10 mm in 10 days. Following osteotomy, ED-71 (0.05 microg/kg) was administered subcutaneously twice a week to the ED-71 group un...
journal_title：Bone
pub_type： 杂志文章
doi：10.1016/s8756-3282(98)00179-3
更新日期：1999-03-01 00:00:00
abstract：:Achondroplasia (ACH) and thanatophoric dysplasia (TD) are human skeletal disorders of increasing severity accounted for by mutations in the fibroblast growth factor receptor 3 (FGFR3). Attempts to elucidate the molecular signaling pathways leading to these phenotypes through mouse model engineering have provided relev...
journal_title：Bone
pub_type： 杂志文章
doi：10.1016/j.bone.2003.09.002
更新日期：2004-01-01 00:00:00
abstract：:The musculoskeletal system is significantly more complex than portrayed by traditional reductionist approaches that have focused on and studied the components of this system separately. While bone and skeletal muscle are the two largest tissues within this system, this system also includes tendons, ligaments, cartilag...
journal_title：Bone
pub_type： 杂志文章,评审
doi：10.1016/j.bone.2015.02.010
更新日期：2015-11-01 00:00:00
abstract：:Radiation of the hip is an established method to prevent heterotopic ossification (HO) following total hip arthroplasty (THA) but the precise mechanism is unclear. As inflammatory processes are suggested to be involved in the pathogenesis of HO, we hypothesized that the preoperative irradiation impacts local immune co...
journal_title：Bone
pub_type： 杂志文章
doi：10.1016/j.bone.2013.03.020
更新日期：2013-07-01 00:00:00
abstract：CONTEXT:Low energy availability causes disruption of hypothalamic gonadotropin-releasing hormone secretion leading to functional hypothalamic amenorrhea (FHA) and hypoestrogenism, which in turn contributes to decreased bone mineral density (BMD) and increased bone marrow adipose tissue (MAT). Transdermal estradiol admi...
journal_title：Bone
pub_type： 杂志文章
doi：10.1016/j.bone.2021.115841
更新日期：2021-01-06 00:00:00
abstract：:The hips are frequently involved in inheritable diseases which affect the bones. The clinical and radiological presentation of these diseases may be very similar to common hip disorders as developmental dysplasia of the hip, osteoarthritis and avascular necrosis, so the diagnosis may be easily overlooked and treatment...
journal_title：Bone
pub_type： 杂志文章,评审
doi：10.1016/j.bone.2020.115729
更新日期：2021-02-01 00:00:00
abstract：PURPOSE:Clinical and in vitro studies suggest that subchondral bone sclerosis due to abnormal osteoblasts is involved in the progression of osteoarthritis (OA). Human osteoblasts isolated from sclerotic subchondral OA bone tissue show an altered phenotype, a decreased canonical Wnt/ß-catenin pathway, and a reduced mine...
journal_title：Bone
pub_type： 杂志文章
doi：10.1016/j.bone.2015.02.001
更新日期：2015-06-01 00:00:00
abstract：:Osteoprogenitors present in cell populations derived from fetal or newborn rat and mouse calvaria differentiate in long term culture and form osteoblastic bone-forming colonies (bone nodules). Previous reports have indicated considerable differences between bone cell populations derived from these two species with reg...
journal_title：Bone
pub_type： 杂志文章
doi：10.1016/s8756-3282(98)00084-2
更新日期：1998-08-01 00:00:00
abstract：:Colony-stimulating factor-1 (CSF-1) induces osteoclast spreading that requires activation of c-Src and phosphatidyl inositol 3-kinase (PI3-K), both of which are recruited to activated c-Fms, the CSF-1 receptor. The present report provides evidence that the hemopoietic guanine nucleotide exchange factor (GEF), Vav, and...
journal_title：Bone
pub_type： 杂志文章
doi：10.1016/j.bone.2006.06.012
更新日期：2006-12-01 00:00:00
abstract：:The uncarboxylated form of the osteoblast-specific secreted molecule osteocalcin is a hormone favoring glucose handling and increasing energy expenditure. As a result, the absence of osteocalcin leads to glucose intolerance in mice, while genetically modified mice with an increase in uncarboxylated osteocalcin are pro...
journal_title：Bone
pub_type： 杂志文章
doi：10.1016/j.bone.2011.04.017
更新日期：2012-02-01 00:00:00
