Abstract:
:Liver X receptors (LXRs) are nuclear receptors that play a crucial role in the transcriptional control of lipid metabolism. Pharmacological LXR activation is an attractive concept for the treatment of atherosclerosis. Genetic LXR deficiency in mice has been shown to have an effect on bone turnover and structure and LXR activation is known to influence the osteogenic differentiation of bone marrow stromal cells. Therefore, therapeutic pharmacological LXR activation may have relevant effects on bone. Here, using two synthetic LXR ligands, T0901317 and GW3965, we investigated the effect of LXR activation on murine osteoblasts and the influence of long-term LXR activation on bone in vivo in mice. Short term (48 h) in vitro treatment of primary murine osteoblasts with T0901317 resulted in a dose-dependent decrease of osteocalcin and alkaline phosphatase mRNA and protein. In vivo, a 6-day treatment of C57BL/6J mice with T0901317 led to a 40% reduction of serum osteocalcin concentrations. Long-term (12-week) oral administration of T0901317 or GW3965 influenced the expression of established LXR target genes in liver and intestine, but did not alter trabecular and cortical bone structure or bone turnover as determined by total skeleton radiography, histomorphometric analysis of lumbar vertebral trabecular bone, micro CT analysis of femur cortical bone and biochemical determination of bone formation and resorption markers. We conclude that short-term pharmacological LXR activation has the potential to profoundly influence osteoblast function, but that long-term LXR activation in vivo has no adverse effects on the murine skeleton.
journal_name
Bonejournal_title
Boneauthors
Prawitt J,Beil FT,Marshall RP,Bartelt A,Ruether W,Heeren J,Amling M,Staels B,Niemeier Adoi
10.1016/j.bone.2010.08.018subject
Has Abstractpub_date
2011-02-01 00:00:00pages
339-46issue
2eissn
8756-3282issn
1873-2763pii
S8756-3282(10)01436-5journal_volume
48pub_type
杂志文章相关文献
BONE文献大全abstract::Parathyroid hormone (PTH) is used clinically in osteoporotic patients to increase bone mass by enhancing bone formation. PTH therapy is not uniformly effective at all skeletal sites and "life-style" factors may modulate the skeletal response to PTH. Alcohol may represent one of these factors. Chronic alcohol abuse is ...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/j.bone.2007.12.221
更新日期:2008-04-01 00:00:00
abstract::We previously reported that osteoclast formation in vitro, by coculture of mouse bone marrow and primary osteoblastic cells, occurs in two phases: proliferation of osteoclast progenitors followed by terminal differentiation into mature osteoclasts. Using this coculture system, we examined the effects of c-fos antisens...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/8756-3282(96)00076-2
更新日期:1996-06-01 00:00:00
abstract::Several studies have shown that treatment with bisphosphonates can reduce the pain associated with different painful diseases. In a previous study we demonstrated that in mice two bisphosponates, clodronate and pamidronate, had an antinociceptive effect under acute conditions not related to bone processes, after in ve...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/s8756-3282(03)00229-1
更新日期:2003-10-01 00:00:00
abstract::Bisphosphonates are one of the most well studied groups of medications and they are bone specific. This tissue specificity is a rare property for a drug introduced into clinical practice as long as 40 years ago. Over the years, the therapeutic boundaries of bisphosphonates were explored and their safety profile has wi...
journal_title:Bone
pub_type: 杂志文章,评审
doi:10.1016/j.bone.2011.01.003
更新日期:2011-07-01 00:00:00
abstract::Many clinical and experimental investigations address the influence of statins on bone formation and fracture healing. Simvastatin was shown to increase the expression of Bone morphogenetic protein (BMP-2), which is one of the most potent growth factors targeting bone formation. In this study, the effect of simvastati...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/j.bone.2009.05.010
更新日期:2009-09-01 00:00:00
abstract::The assessment of fracture risk often relies primarily on measuring bone mineral density, thereby accounting for only a single pathology: the loss of bone mass. However, bone's ability to resist fracture is a result of its biphasic composition and hierarchical structure that imbue it with high strength and toughness. ...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/j.bone.2016.03.013
更新日期:2016-06-01 00:00:00
abstract::The role of vitamin D receptor (VDR) gene polymorphisms in the determination of bone mass and bone turnover is controversial in women. The aim of the study was to determine whether VDR polymorphisms are associated with indices of bone mineral density (BMD) (by dual-energy X-ray absorptiometry and by ultrasound) and/or...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/s8756-3282(02)00867-0
更新日期:2002-11-01 00:00:00
abstract::Nearly all bone fractures in humans can deteriorate into a non-union fracture, often due to formation of fibrotic tissue. Cranial allogeneic bone grafts present a striking example: although seemingly attractive for craniofacial reconstructions, they often fail due to fibrosis at the host-graft junction, which physical...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/j.bone.2017.01.020
更新日期:2017-04-01 00:00:00
abstract::Osteoclastic bone degradation depends on the activity of several proteolytic enzymes, in particular to those belonging to the classes of cysteine proteinases and matrix metalloproteinases (MMPs). Yet, several findings suggest that the two types of plasminogen activators (PA), the tissue- and urokinase-type PA (tPA and...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/j.bone.2008.07.004
更新日期:2008-11-01 00:00:00
abstract::Osteocytes form over 90% of the bone cells and are postulated to be mechanosensors responsible for regulating the function of osteoclasts and osteoblasts in bone modeling and remodeling. Physical activity results in mechanical loading on the bones. Osteocytes are thought to be the main mechanosensory cells in bone. Up...
journal_title:Bone
pub_type: 杂志文章,评审
doi:10.1016/j.bone.2020.115328
更新日期:2020-08-01 00:00:00
abstract::Interleukin-1 (IL-1) has been shown to promote osteoclast (OC) differentiation, in addition to acting as a survival factor for mature osteoclasts. In this study, we investigate the expression of IL-1 during human osteoclast formation, taking advantage of a recently reported in vitro culture system that generates human...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/s8756-3282(99)00176-3
更新日期:1999-09-01 00:00:00
abstract::Chronic inflammatory diseases are associated with bone loss. While the occurrence of systemic bone loss is well described in chronic inflammatory diseases, the impact of these conditions on articular bone has not been systematically investigated. Recent refinements in high-resolution CT assessment of the joints now al...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/j.bone.2018.07.017
更新日期:2018-11-01 00:00:00
abstract::To investigate whether exercise training can produce increases in bone mass in spinal cord-injured (SCI) individuals with established disuse osteopenia, nine subjects (age 28.2 years, time since injury 6.0 years, level of injury C5-T7) were recruited for a 9-month training program using functional electrical stimulati...
journal_title:Bone
pub_type: 临床试验,杂志文章
doi:10.1016/8756-3282(96)00109-3
更新日期:1996-07-01 00:00:00
abstract::Using immunohistology with two specific antisera raised against N-terminal parathyroid hormone-related protein (PTHrP) and in situ hybridization (riboprobe to common coding exon), evidence is provided for the expression of PTHrP by mouse, rabbit, and human osteoclasts derived from several in vitro and in vivo sources....
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/s8756-3282(97)00278-0
更新日期:1998-03-01 00:00:00
abstract::Cancer chemotherapy often causes significant bone loss, marrow adiposity and haematopoietic defects, yet the underlying mechanisms and recovery potential remain unclear. Wnt/β-catenin signalling is integral to the regulation of osteogenesis, adipogenesis and haematopoiesis; using a rat model, the current study investi...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/j.bone.2012.03.027
更新日期:2012-06-01 00:00:00
abstract::Bone fragility is a complication of chronic kidney disease (CKD). Patients on dialysis have higher risk of fracture than the general population, but the reason remains obscure. Bone strength is determined by bone mass and bone quality. Although factors affecting bone quality include microarchitecture, remodeling activ...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/j.bone.2011.03.672
更新日期:2011-06-01 00:00:00
abstract::Skeletal problems and osteoporosis occur in up to 50% affected neurofibromatosis type 1 (NF1) humans. Inactivation of neurofibromin results in deregulation of Ras signal transduction. Little is known of bone biology in humans with NF1. The goal of our work was to determine if loss-of-function of Nf1 gene was associate...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/j.bone.2005.01.022
更新日期:2005-05-01 00:00:00
abstract::Bone marrow mesenchymal stem cells (BMMSCs) provide the biological basis for bone reconstruction. Mechanical tension stimulation as a potent modulator is able to promote osteogenic capability of BMMSCs. Long non-coding RNAs (LncRNAs) as competing endogenous RNAs (ceRNAs) for microRNAs, are postulated to regulate the o...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/j.bone.2017.12.013
更新日期:2018-03-01 00:00:00
abstract::Much is known about skeletal adaptation in relation to the mechanical functions that bones serve. This includes how bone adapts to mechanical loading during an individual's lifetime as well as over evolutionary time. Although controlled loading in animal models allows us to observe short-term bone adaptation (epigenet...
journal_title:Bone
pub_type: 杂志文章,评审
doi:10.1016/j.bone.2019.115114
更新日期:2020-02-01 00:00:00
abstract:BACKGROUND:Preterm infants are at risk for impaired bone mineralization and growth in length later in life due to inadequate nutritional intake in the early postnatal period. OBJECTIVE:To investigate whether increased nutritional supplementation of calcium, phosphate and protein in Very Low Birth Weight (VLBW) infants...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/j.bone.2017.12.022
更新日期:2018-03-01 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:INTRODUCTION:Alström syndrome (ALMS) is an ultra-rare metabolic disorder caused by biallelic loss-of-function in the Alms1 gene which encodes a ubiquitously expressed centrosomal protein of the primary cilium. Although ALMS is characterised by several metabolic and hormonal dysfunctions that can lead to an increased ri...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/j.bone.2020.115756
更新日期:2021-02-01 00:00:00
abstract::Immobilization leads to rapid loss of bone mass and mechanical competence, and long-term immobilization or repeated periods of short-term immobilization can have serious skeletal consequences and may lead to increased fracture liability. The aim of the present preclinical study was, therefore, to assess whether two an...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/s8756-3282(00)00375-6
更新日期:2000-11-01 00:00:00
abstract::Genetic mouse models are widely used for understanding human diseases but we know much less about the anatomical structure of the auditory ossicles in the mouse than we do about human ossicles. Furthermore, current studies have mainly focused on disease conditions such as osteomalacia and rickets in patients with hypo...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/j.bone.2017.06.007
更新日期:2017-10-01 00:00:00
abstract::Due to the rising life expectancy, bone diseases (e.g. osteoporosis, osteoarthritis) and trauma (e.g. fracture) have become an important socio-economic burden. Accurate visualization and quantification of the bone microstructure in vivo is seen as an important step to enhance diagnosis and treatment. Micro-computed to...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/j.bone.2018.06.006
更新日期:2018-09-01 00:00:00
abstract::The purpose was to investigate whether the reduction in bone mechanical strength induced by immobilization could be prevented by a bisphosphonate compound, clodronate. The torsional breaking strength of the tibia was measured using a specially constructed torsion machine. Maximum torque capacity, maximum angle of defo...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/8756-3282(94)90302-6
更新日期:1994-05-01 00:00:00
abstract:BACKGROUND:Fibrodysplasia ossificans progressiva (FOP) is a catastrophic genetic disorder of progressive heterotopic ossification (HO). Assessment of functional mobility in FOP will be essential to support clinical trials of investigational agents. RESULTS:Of necessity, we developed a simple, rapidly-administered, cum...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/j.bone.2017.04.015
更新日期:2017-08-01 00:00:00
abstract::Bisphosphonate (BP)-related osteonecrosis of the jaw, previously known as BRONJ, now referred to more broadly as medication-related osteonecrosis of the jaw (MRONJ), is a morbid condition that represents a significant risk for oncology patients who have received high dose intravenous (IV) infusion of a potent nitrogen...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/j.bone.2019.03.027
更新日期:2019-06-01 00:00:00
abstract:OBJECTIVES:Osteoporosis results in loss of bone mass and microarchitectural deterioration. Dental radiographs potentially offer a means of screening for osteoporosis as they are commonly made on adults. Spatial frequency analyses are well suited to detect subtle changes in image patterns. We hypothesize that individual...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/j.bone.2004.03.002
更新日期:2004-08-01 00:00:00
abstract::Cartilage canals are temporary vessel-containing structures within the growth cartilage. The canals gradually regress with age in a process designated chondrification, where the content of the canals is replaced by cartilage. The process of chondrification is considered physiological; however, premature regression has...
journal_title:Bone
pub_type: 杂志文章
doi:10.1016/j.bone.2004.08.016
更新日期:2004-12-01 00:00:00