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) was used to treat 9-week-old female Dkk1 KO (Dkk1-/-:Wnt3+/-) mice and compared to Scl-Ab-treated wild-type mice as well as vehicle-treated Dkk1 KO and wild-type animals. While Wnt3 heterozygote (Wnt3+/-) mice show no bone phenotype, Scl-Ab and vehicle-treated control groups of this genotype were included. Specimens were harvested after 3 weeks for microCT, bone histomorphometry, anti-sclerostin immunohistochemistry, and biomechanical testing. Scl-Ab enhanced bone anabolism in all treatment groups, but with synergistic enhancement seen in the cancellous compartment of Dkk1 KO mice (bone volume + 55% Dkk1 KO p < 0.01; + 22% wild type p < 0.05). Scl-Ab treatment produced less marked increases in cortical bone of the tibiae, with anabolic effects similar across genotypes. Mechanical testing confirmed that Scl-Ab improved strength across all genotypes; however, no enhancement was seen within Dkk1 KO mice. Dynamic bone labeling showed that Scl-Ab treatment was associated with increased bone formation, regardless of genotype. Immunohistochemical staining for sclerostin protein indicated no differences in the Dkk1 KO mice, indicating that the increased Wnt signaling associated with DKK1 deficiency was not compensated by upregulation of sclerostin protein. These data suggest complex interactions between Wnt signaling factors in bone, but critically illustrate synergy between DKK1 deficiency and Scl-Ab treatment. These data support the application of dual-targeted therapeutics in the modulation of bone anabolism.
journal_name
Calcif Tissue Intjournal_title
Calcified tissue internationalauthors
Morse A,Cheng TL,Schindeler A,McDonald MM,Mohanty ST,Kneissel M,Kramer I,Little DGdoi
10.1007/s00223-018-0420-6subject
Has Abstractpub_date
2018-09-01 00:00:00pages
298-310issue
3eissn
0171-967Xissn
1432-0827pii
10.1007/s00223-018-0420-6journal_volume
103pub_type
杂志文章abstract::To characterize osteopenic changes in ovariectomized (OVX) rats as a function of time, female Sprague Dawley rats (240 g body weight, 90 days old) were subjected to bilateral ovariectomy or sham surgery and killed at various times from 14-180 days postovariectomy. The proximal tibial metaphysis was processed undecalci...
journal_title:Calcified tissue international
pub_type: 杂志文章
doi:10.1007/BF02571317
更新日期:1988-09-01 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::This manuscript discusses mineral and bone disorders of chronic kidney disease (MBD-CKD) in pediatric patients with special emphasis on the underlying pathophysiology, the causes and clinical profile of growth retardation, the alterations in the growth plate, the strategies to optimize growth and the medical recommend...
journal_title:Calcified tissue international
pub_type: 杂志文章,评审
doi:10.1007/s00223-020-00787-z
更新日期:2021-01-16 00:00:00
abstract::Compressive strength index (CSI) of the femoral neck is a parameter that integrates the information of bone mineral density (BMD), femoral neck width (FNW), and body weight. CSI is considered to have the potential to improve the performance of assessment for hip fracture risk. However, studies on CSI have been rare. I...
journal_title:Calcified tissue international
pub_type: 杂志文章
doi:10.1007/s00223-010-9406-8
更新日期:2010-10-01 00:00:00
abstract::A comparative polarized light (PLM), scanning (SEM), and transmission (TEM) electron microscopy study was carried out on cross- and longitudinal sections of human lamellar bone in the tibiae of four male subjects aged 9, 23, 45, and 70 years. SEM analysis was also performed on rectangular-prismatic samples in order to...
journal_title:Calcified tissue international
pub_type: 杂志文章
doi:10.1007/BF01673402
更新日期:1993-01-01 00:00:00
abstract::This article reviews the effects of restrictive eating disorders on bone health. The relationship between eating disorders and amenorrhea is discussed in detail. The pathologic impact of malnutrition on bone is explored by examining the results of studies using various available imaging techniques. The multiple hormon...
journal_title:Calcified tissue international
pub_type: 杂志文章,评审
doi:10.1007/s00223-016-0164-0
更新日期:2017-05-01 00:00:00
abstract::To assess the reductions in bone mass, strength, and turnover in adjuvant-induced arthritic rats and to examine the effect of a new benzamide compound, DU-6712, on these parameters, a 28-day dosing experiment was performed using 8-week-old female Lewis rats. Arthritis was induced by injecting the adjuvant into the hin...
journal_title:Calcified tissue international
pub_type: 杂志文章
doi:10.1007/s002239900472
更新日期:1998-06-01 00:00:00
abstract::The increased uptake of bone-seeking radionuclides following a fracture has been stated to be due to an increase in bone blood flow, resulting in an increase in capillary surface area available for exchange. This paper examines the relationship between the maximum instantaneous extraction of 99mTc-MDP and blood flow i...
journal_title:Calcified tissue international
pub_type: 杂志文章
doi:10.1007/BF02405085
更新日期:1983-07-01 00:00:00
abstract::In order to study in detail the processes leading to the resorption and ankylosis of teeth after trauma, the effects of cold application on the periodontal tissues were studied in the mouse. Liquid nitrogen was applied locally to the outer surface of the lower jaw which resulted in a freezing of the incisor and its su...
journal_title:Calcified tissue international
pub_type: 杂志文章
doi:10.1007/BF02555735
更新日期:1986-07-01 00:00:00
abstract::The objective of this study was to compare the bone mineral density (BMD) of men with Down syndrome (DS) to otherwise mentally retarded (MR) men and to investigate whether leg muscle strength of these patients is related to BMD. Two groups with MR (with and without DS) participated in the study, having met the followi...
journal_title:Calcified tissue international
pub_type: 杂志文章
doi:10.1007/s002230010035
更新日期:2000-03-01 00:00:00
abstract::Noncarious cervical lesions have a multifactorial etiology. Mechanical stress has been identified as one of the factors, but little evidence exists for its cause-effect relationship. This study was conducted at three different pH levels to observe the surface loss on dentin beams under tension and compression. Bovine ...
journal_title:Calcified tissue international
pub_type: 杂志文章
doi:10.1007/s00223-005-0271-9
更新日期:2006-12-01 00:00:00
abstract::In order to investigate the pathogenesis of ossification of the posterior longitudinal ligament (OPLL) of the spine, we examined the distribution of insulin-like growth factor I (IGF-I) in the posterior longitudinal ligaments of OPLL patients, and analyzed the effects of IGF-I on the cultured spinal ligament cells. Fo...
journal_title:Calcified tissue international
pub_type: 杂志文章
doi:10.1007/s002239900410
更新日期:1998-02-01 00:00:00
abstract::The bone mineral density (BMD) of the radius and spine was determined by photo absorptiometry in a large number of controls (radius: n = 111; spine: n = 85; age range: 50-79 years) and osteoporotic women (radius: n = 98; spine n = 140; age range: 50-79 years) with at least one "atraumatic" vertebral compression fractu...
journal_title:Calcified tissue international
pub_type: 杂志文章
doi:10.1007/BF02554998
更新日期:1990-04-01 00:00:00
abstract::The tumor-suppressor p53 is a transcription factor that regulates a number of genes in the process of cell-cycle inhibition, apoptosis, and DNA damage. Recent studies have revealed a crucial role for p53 in bone remodeling. In our previous studies we have shown that p53 is an important regulator of osteoblast differen...
journal_title:Calcified tissue international
pub_type: 杂志文章
doi:10.1007/s00223-011-9533-x
更新日期:2011-11-01 00:00:00
abstract::The European Forsteo Observational Study was designed to examine the effectiveness of teriparatide in postmenopausal women with osteoporosis treated for up to 18 months in normal clinical practice in eight European countries. The incidence of clinical vertebral and nonvertebral fragility fractures, back pain, and heal...
journal_title:Calcified tissue international
pub_type: 杂志文章
doi:10.1007/s00223-009-9299-6
更新日期:2009-12-01 00:00:00
abstract::The present report compares the effects of different membrane phospholipid (PL)-cholesterol compositions on the kinetics of liposome-mediated formation of calcium phosphates from metastable solutions (2.25 mM CaCl2; 1.5 mM KH2PO4) at 22 degrees C, pH 7.4 and 240 mOsm. In most experiments, the liposomes were composed o...
journal_title:Calcified tissue international
pub_type: 杂志文章
doi:10.1007/BF00296290
更新日期:1992-03-01 00:00:00
abstract::Raf-1, the product of proto-oncogene c-raf-1, has key roles in the signal transduction pathways within the cell. The molecular mechanisms of tooth development in the mouse embryo are not known in detail. We examined the expression of Raf-1 during subsequent tooth development by immunohistochemical analysis. In mouse e...
journal_title:Calcified tissue international
pub_type: 杂志文章
doi:10.1007/BF02509547
更新日期:1996-01-01 00:00:00
abstract::We measured serum concentrations of bone Gla-protein (osteocalcin, BGP) and carboxyterminal propeptide of type I procollagen (PICP) in 14 patients with active acromegaly. Blood was collected at 0800 for measurement of bone Gla-protein (BGP), carboxyterminal propeptide of type I procollagen (PICP), and insulin-like gro...
journal_title:Calcified tissue international
pub_type: 杂志文章
doi:10.1007/BF00298716
更新日期:1993-03-01 00:00:00
abstract::This study examines the efficacy of using radiolabeled thymidine as a measure of bone cell DNA synthesis. The effect of a bone-active peptide on cell proliferation is assessed under different labeling conditions and it is shown that the apparent stimulation in DNA synthesis is due to an increase in participating cells...
journal_title:Calcified tissue international
pub_type: 杂志文章
doi:10.1007/BF02553298
更新日期:1986-08-01 00:00:00
abstract::Although several observational studies have demonstrated an association between vitamin K status and bone mineral density (BMD) in postmenopausal women, no placebo-controlled intervention trials of the effect of vitamin K1 supplementation on bone loss have been reported thus far. In the trial presented here we have in...
journal_title:Calcified tissue international
pub_type: 临床试验,杂志文章,随机对照试验
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abstract::Studies of the effect of parathyroidectomy (PTX) on bone turnover in patients with the combination of primary hyperparathyroidism (PHPT) and Paget's disease (PD) are largely limited to case reports. The etiology of the combination is disputed. We report 30 patients and their biochemical (n = 17) and histomorphometric ...
journal_title:Calcified tissue international
pub_type: 杂志文章
doi:10.1007/s002239900728
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journal_title:Calcified tissue international
pub_type: 杂志文章
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abstract::To experimentally examine the participation of amelogenins in controlled mineral-phase maturation of mammalian enamel, the identification of the individual proteins and their corresponding gene(s) is required. For this purpose, cDNAs were constructed from polyadenylated RNA from 2-day postnatal murine teeth, molecular...
journal_title:Calcified tissue international
pub_type: 杂志文章
doi:10.1007/BF02556627
更新日期:1987-04-01 00:00:00
abstract::Several rare inherited disorders have been described that show phenotypic overlap with Paget's disease of bone (PDB) and in which PDB is a component of a multisystem disorder affecting muscle and the central nervous system. These conditions are the subject of this review article. Insertion mutations within exon 1 of t...
journal_title:Calcified tissue international
pub_type: 杂志文章,评审
doi:10.1007/s00223-019-00520-5
更新日期:2019-05-01 00:00:00
abstract::Bone is a dynamic tissue that is able to sense and adapt to mechanical stimuli by modulating its mass, geometry, and structure. Bone marrow stromal cells (BMSCs) are known to play an integral part in bone formation by providing an osteoprogenitor cell source capable of differentiating into mature osteoblasts in respon...
journal_title:Calcified tissue international
pub_type: 杂志文章
doi:10.1007/s00223-003-0104-7
更新日期:2004-05-01 00:00:00
abstract::The purpose of the present work was to investigate the appearance of ossification centers in human femur by Dual-energy X-ray Absorptiometry (DXA), comparing densitometric data with morphogenetic events. Posteroanterior scans were performed on 31 dried femora (from 11.5 weeks of conceptual age to 1 year of postnatal l...
journal_title:Calcified tissue international
pub_type: 杂志文章
doi:10.1007/pl00005841
更新日期:2000-04-01 00:00:00
abstract::To clarify the mechanisms underlying shockwave-induced osteogenesis, we applied shockwave to rat femoral shafts from the ventral side. We assessed bone mineral content (BMC) and bone mineral density (BMD), and analyzed the spatial and temporal gene expression for pro-alpha1 (I) collagen (COL1A1), pro-alpha1 (II) colla...
journal_title:Calcified tissue international
pub_type: 杂志文章
doi:10.1007/s00223-003-0043-3
更新日期:2004-02-01 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::Whether the decrease of zinc content in the femoral-metaphyseal tissues of rats with skeletal unloading is involved in the alteration of bone metabolism was investigated. Skeletal unloading was designed using the model of hindlimb suspension in rats. Animals were fed for 4 days with the unloading. The metaphyseal zinc...
journal_title:Calcified tissue international
pub_type: 杂志文章
doi:10.1007/BF00310262
更新日期:1995-09-01 00:00:00
abstract::The effect of parathormone (PTH), lipopolysaccharide (LPS), or interleukin-1 (IL-1) on calcium release and collagen degradation in bone was examined in vitro using labeled neonatal calvaria of normal mice and also of osteopetrotic microphthalmic (mi/mi) mice that have defective osteoclasts. All three agents stimulated...
journal_title:Calcified tissue international
pub_type: 杂志文章
doi:10.1007/BF02554878
更新日期:1985-05-01 00:00:00