当前位置： SCI文献检索 > BONE期刊下所有文献 > Inhibition of bone resorption by the cathepsin K inhibitor odanacatib is fully reversible.

Inhibition of bone resorption by the cathepsin K inhibitor odanacatib is fully reversible.

Abstract：

:The cathepsin K (CatK) inhibitor odanacatib (ODN) is currently being developed for the treatment of osteoporosis. In clinical trials, efficacy and resolution of effect of ODN treatment on bone turnover biomarkers and accrued bone mass have been demonstrated. Here, we examine the effects of continuing treatment and discontinuation of ODN versus alendronate (ALN) on osteoclast (OC) function. First, accessibility and reversible engagement of active CatK in intracellular vesicles and resorption lacunae of actively resorbing OCs were demonstrated by the selective and reversible CatK inhibitors, BODIPY-L-226 (IC50=39nM) and L-873,724 (IC50=0.5nM). Next, mature human OCs on bone slices were treated with vehicle, ODN, or ALN for 2days, followed by either continuing with the same treatment, or replacement of the inhibitors by vehicle for additional times as specified per experimental conditions. Maintaining OCs on ODN or ALN significantly reduced CTx-I release compared to vehicle controls. However, only the treatment of OCs with ODN resulted in the formation of small shallow discrete resorption pits, retention of intracellular vesicles enriched with CatK and other lysosomal enzymes, increase in 1-CTP release and number of TRAP(+) OCs. Upon discontinuation of ODN treatment, OCs rapidly resumed bone resorption activity, as demonstrated by a return of OC functional markers (CTx-I, 1-CTP), cell number and size, morphology and number of resorption pits, and vesicular secretion of CatK toward the respective vehicle levels. As expected, discontinuation of ALN did not reverse the treatment-related inhibition of OC activity in the time frame of the experiment. In summary, this study demonstrated rapid kinetics of inhibition and reversibility of the effects of ODN on OC bone resorption, that differentiated the cellular mechanism of CatK inhibition from that of the bisphosphate antiresorptive ALN.

journal_name

Bone

journal_title

Bone

authors

Zhuo Y,Gauthier JY,Black WC,Percival MD,Duong LT

doi

10.1016/j.bone.2014.07.013

subject

Has Abstract

pub_date

2014-10-01 00:00:00

pages

269-80

eissn

8756-3282

issn

1873-2763

pii

S8756-3282(14)00265-8

journal_volume

67

pub_type

杂志文章

相关文献

BONE文献大全
  • Increased prevalence of fractures in inadequately transfused and chelated Indian children and young adults with beta thalassemia major.

    abstract：INTRODUCTION:In patients with beta thalassemia major, inadequate transfusion and chelation may compromise bone health and increase risk of fractures. The objective of this study was to describe the prevalence of fractures in Indian inadequately transfused and chelated children, adolescents and young adults with beta th...

    journal_title：Bone

    pub_type： 杂志文章

    doi：10.1016/j.bone.2020.115649

    authors： Ekbote V,Padidela R,Khadilkar V,Ramanan V,Maheshwari A,Mughal Z,Kariki EP,Crabtree N,Khadilkar A

    更新日期：2021-02-01 00:00:00

  • Photo-cured hyaluronic acid-based hydrogels containing growth and differentiation factor 5 (GDF-5) for bone tissue regeneration.

    abstract：:In this study we describe the generation and influences on in vitro and in vivo osteogenesis of photo-cured hyaluronic acid (HA) hydrogels loaded with growth and differentiation factor 5 (GDF-5). Prior to loading GDF-5, we characterized the release profiles from these hydrogels and tested their respective cell viabili...

    journal_title：Bone

    pub_type： 杂志文章

    doi：10.1016/j.bone.2013.11.019

    authors： Bae MS,Ohe JY,Lee JB,Heo DN,Byun W,Bae H,Kwon YD,Kwon IK

    更新日期：2014-02-01 00:00:00

  • Computational finite element bone mechanics accurately predicts mechanical competence in the human radius of an elderly population.

    abstract：:High-resolution peripheral quantitative computed tomography (HR-pQCT) is clinically available today and provides a non-invasive measure of 3D bone geometry and micro-architecture with unprecedented detail. In combination with microarchitectural finite element (μFE) models it can be used to determine bone strength usin...

    journal_title：Bone

    pub_type： 杂志文章

    doi：10.1016/j.bone.2011.02.022

    authors： Mueller TL,Christen D,Sandercott S,Boyd SK,van Rietbergen B,Eckstein F,Lochmüller EM,Müller R,van Lenthe GH

    更新日期：2011-06-01 00:00:00

  • Treatment with risedronate or alendronate prevents hind-limb immobilization-induced loss of bone density and strength in adult female rats.

    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

    authors： Mosekilde L,Thomsen JS,Mackey MS,Phipps RJ

    更新日期：2000-11-01 00:00:00

  • Changes in chemical composition of cortical bone associated with bone fragility in rat model with chronic kidney disease.

    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

    authors： Iwasaki Y,Kazama JJ,Yamato H,Fukagawa M

    更新日期：2011-06-01 00:00:00

  • Paradoxical Sost gene expression response to mechanical unloading in metaphyseal bone.

    abstract：:The Sost gene encodes Sclerostin, an inhibitor of Wnt-signaling, generally considered a main response gene to mechanical loading in bone. Several papers describe that unloading leads to upregulation of Sost, which in turn may lead to loss of bone. These studies were based on whole bone homogenates or cortical bone. By...

    journal_title：Bone

    pub_type： 杂志文章

    doi：10.1016/j.bone.2013.01.018

    authors： Macias BR,Aspenberg P,Agholme F

    更新日期：2013-04-01 00:00:00

  • Impaired bone healing pattern in mice with ovariectomy-induced osteoporosis: A drill-hole defect model.

    abstract：OBJECTIVE:To establish a drill-hole defect model in osteoporotic mouse femur by comparing temporal cortical bone healing pattern between OVX-induced osteoporotic bone and sham-operated bone. METHODS:3-month-old female C57BL/6 mice were randomly divided into an ovariectomy group (OVX) and a sham-operated group (Sham). ...

    journal_title：Bone

    pub_type： 杂志文章

    doi：10.1016/j.bone.2011.03.720

    authors： He YX,Zhang G,Pan XH,Liu Z,Zheng LZ,Chan CW,Lee KM,Cao YP,Li G,Wei L,Hung LK,Leung KS,Qin L

    更新日期：2011-06-01 00:00:00

  • Osteocalcin, adipokines and their associations with glucose metabolism in type 1 diabetes.

    abstract：:To determine osteocalcin (OC) and adipokines in type 1 diabetes (T1D) and healthy controls, and to explore possible associations between glucose and bone metabolism, body composition and adipokines. Serum levels of total OC, undercarboxylated (UC-OC), leptin, adiponectin, and other parameters of glucose and bone metab...

    journal_title：Bone

    pub_type： 杂志文章

    doi：10.1016/j.bone.2015.04.017

    authors： Neumann T,Lodes S,Kästner B,Franke S,Kiehntopf M,Lehmann T,Müller UA,Wolf G,Sämann A

    更新日期：2016-01-01 00:00:00

  • Cancer cell foraging to explain bone-specific metastatic progression.

    abstract：:Metastatic cancer is lethal and patients who suffer bone metastases fare especially poorly. Bone-specific metastatic progression in prostate and breast cancers is a highly observed example of organ-specific metastasis, or organotropism. Though research has delineated the sequential steps of the metastatic cascade, the...

    journal_title：Bone

    pub_type： 杂志文章

    doi：10.1016/j.bone.2020.115788

    authors： Mallin MM,Pienta KJ,Amend SR

    更新日期：2020-12-03 00:00:00

  • Age at first oral contraceptive use as a major determinant of vertebral bone mass in female endurance athletes.

    abstract：:It was the aim of this retrospective analysis to examine the influence of low-dose monophasic oral contraceptives (OCs) on bone mineral density (BMD) of the femoral neck and of the spine in young female endurance athletes. Data on training intensity, dietary intake, menarche, menstrual cycle disorders, years of OC use...

    journal_title：Bone

    pub_type： 杂志文章

    doi：10.1016/j.bone.2004.05.017

    authors： Hartard M,Kleinmond C,Kirchbichler A,Jeschke D,Wiseman M,Weissenbacher ER,Felsenberg D,Erben RG

    更新日期：2004-10-01 00:00:00

  • The Conneulor: unbiased estimation of connectivity using physical disectors under projection.

    abstract：:The Euler number and the connectivity of an arbitrary object is defined, and it is illustrated why the connectivity of an n-dimensional object cannot be estimated in an (n-1)-dimensional section. The disector--principle for 3-D counting of the Euler--events is illustrated in cancellous bone. The correct handling for u...

    journal_title：Bone

    pub_type： 杂志文章

    doi：10.1016/8756-3282(93)90144-y

    authors： Gundersen HJ,Boyce RW,Nyengaard JR,Odgaard A

    更新日期：1993-05-01 00:00:00

  • How can bone turnover modify bone strength independent of bone mass?

    abstract：:The amount of bone turnover in the skeleton has been identified as a predictor of fracture risk independent of areal bone mineral density (aBMD) and is increasingly cited as an explanation for discrepancies between areal bone mineral density and fracture risk. A number of mechanisms have been proposed to explain how b...

    journal_title：Bone

    pub_type： 杂志文章,评审

    doi：10.1016/j.bone.2008.02.001

    authors： Hernandez CJ

    更新日期：2008-06-01 00:00:00

  • Expression of mouse HtrA1 serine protease in normal bone and cartilage and its upregulation in joint cartilage damaged by experimental arthritis.

    abstract：:Levels of HtrA1 protein in cartilage have been reported to elevate in joints of human osteoarthritis patients. To understand roles of HtrA1 in normal osteogenesis as well as in pathogenesis of arthritis, we examine HtrA1 expression pattern during bone and cartilage development and in articular cartilage affected by ex...

    journal_title：Bone

    pub_type： 杂志文章

    doi：10.1016/j.bone.2005.03.015

    authors： Tsuchiya A,Yano M,Tocharus J,Kojima H,Fukumoto M,Kawaichi M,Oka C

    更新日期：2005-09-01 00:00:00

  • Evidence for secular change in Paget's disease.

    abstract：:Death certification data has shown that death rates due to Paget's disease of bone and osteosarcoma in older people (assumed to be attributable to Paget's) declined in the latter part of the 19th and in the early 20th century, suggesting that there may be a secular trend toward less severe disease. We have reviewed a ...

    journal_title：Bone

    pub_type： 杂志文章

    doi：10.1016/s8756-3282(96)00310-9

    authors： Cundy T,McAnulty K,Wattie D,Gamble G,Rutland M,Ibbertson HK

    更新日期：1997-01-01 00:00:00

  • Unbiased estimation of vertebral trabecular connectivity in calcium-restricted ovariectomized minipigs.

    abstract：:The topological changes in vertebral cancellous bone were estimated in vertebrae from calcium-restricted ovariectomized Sinclair S-1 minipigs, a recently described animal model of cancellous osteopenia. Connectivity was estimated using unbiased stereological principles in disector pairs of sections from the first lumb...

    journal_title：Bone

    pub_type： 杂志文章

    doi：10.1016/8756-3282(95)00116-u

    authors： Boyce RW,Ebert DC,Youngs TA,Paddock CL,Mosekilde L,Stevens ML,Gundersen HJ

    更新日期：1995-06-01 00:00:00

  • Candidate 56 and 58 kDa protein(s) responsible for mediating the renal defects in oncogenic hypophosphatemic osteomalacia.

    abstract：:The effects of tumor-conditioned media (TCM) derived from cultured cells from an oncogenic hypophosphatemic osteomalacia (OHO) tumor on transformed human kidney cells were investigated. Dose-dependent cell detachment and aggregation occurred in kidney cells cultured in serum-free medium supplemented with TCM, but not ...

    journal_title：Bone

    pub_type： 杂志文章

    doi：10.1016/8756-3282(95)00458-0

    authors： Rowe PS,Ong AC,Cockerill FJ,Goulding JN,Hewison M

    更新日期：1996-02-01 00:00:00

  • Relationships between marrow fat and bone turnover in ovariectomized and intact rats.

    abstract：:It is known that marrow fat content increases in a variety of osteoporoses. This study sought to clarify this phenomenon by combining bone and marrow histomorphometry, and to determine (1) whether the marrow fat increase follows or precedes diminishment of bone volume, and (2) whether the increase in fat volume is due...

    journal_title：Bone

    pub_type： 杂志文章

    doi：10.1016/8756-3282(91)90011-7

    authors： Martin RB,Zissimos SL

    更新日期：1991-01-01 00:00:00

  • Variations of SOST mRNA expression in human bone are associated with DNA polymorphism and DNA methylation in the SOST gene.

    abstract：:SOST encodes sclerostin, an inhibitor of bone formation that antagonizes canonical Wnt signaling. Variations of SOST expression have an impact on bone mineral density (BMD) and bone strength. We hypothesized that genetic and epigenetic DNA modifications have an impact on SOST gene expression. By analyzing 43 bone samp...

    journal_title：Bone

    pub_type： 杂志文章

    doi：10.1016/j.bone.2016.08.004

    authors： Lhaneche L,Hald JD,Domingues A,Hannouche D,Delepine M,Zelenika D,Boland A,Ostertag A,Cohen-Solal M,Langdahl BL,Harsløf T,de Vernejoul MC,Geoffroy V,Jehan F

    更新日期：2016-11-01 00:00:00

  • Reference intervals of biochemical bone turnover markers for Saudi Arabian women: a cross-sectional study.

    abstract：:Biochemical bone turnover markers (BTMs) provide important information on the diagnosis, therapy and monitoring of metabolic bone diseases including osteoporosis. One goal of antiresorptive therapy in women is to decrease biochemical BTMs to the lower half of reference intervals for healthy pre-menopausal counterparts...

    journal_title：Bone

    pub_type： 杂志文章

    doi：10.1016/j.bone.2010.07.017

    authors： Ardawi MS,Maimani AA,Bahksh TA,Rouzi AA,Qari MH,Raddadi RM

    更新日期：2010-10-01 00:00:00

  • Cortical thickness relative to the transverse diameter of third metacarpal bone reflects bone mineral density in patients with rheumatoid arthritis.

    abstract：OBJECTIVE:Rheumatoid arthritis (RA) is accompanied by potential risk of bone mineral loss. In this study, we developed a screening index for the osteoporosis related level of bone mineral density loss for RA patients as a substitute to the dual-energy X-ray absorptiometry (DXA) method. METHODS:X-ray pictures of both s...

    journal_title：Bone

    pub_type： 杂志文章

    doi：10.1016/j.bone.2020.115405

    authors： Yoshii I,Akita K

    更新日期：2020-08-01 00:00:00

  • Identification of Sparus aurata bone morphogenetic protein 2: molecular cloning, gene expression and in silico analysis of protein conserved features in vertebrates.

    abstract：:Bone morphogenetic protein 2 (BMP-2) is a secreted signaling molecule that acts as an inducer of bone formation and a regulator of embryonic development. The objectives of this work were as follows: (1) to clone the full-length cDNA of BMP-2 in a marine fish model, (2) analyze its gene expression during development, i...

    journal_title：Bone

    pub_type： 杂志文章

    doi：10.1016/j.bone.2006.06.021

    authors： Rafael MS,Laizé V,Cancela ML

    更新日期：2006-12-01 00:00:00

  • Discordant recovery of bone mass and mechanical properties during prolonged recovery from disuse.

    abstract：:Profound bone loss at weight bearing sites is a primary effect of long-duration spaceflight. Moreover, a significant increase in estimated fracture risk remains even 1 year after returning to Earth; hence, it is important to define how quickly bone integrity can recover following prolonged disuse. This study character...

    journal_title：Bone

    pub_type： 杂志文章

    doi：10.1016/j.bone.2012.09.021

    authors： Shirazi-Fard Y,Kupke JS,Bloomfield SA,Hogan HA

    更新日期：2013-01-01 00:00:00

  • Finite element models predict in vitro vertebral body compressive strength better than quantitative computed tomography.

    abstract：:The correlation between bone mineral density and vertebral strength is not based on mechanical principles and thus the method cannot reflect the effects of subtle geometric features and densitometric inhomogeneities that may substantially affect vertebral strength. Finite element models derived from quantitative compu...

    journal_title：Bone

    pub_type： 杂志文章

    doi：10.1016/s8756-3282(03)00210-2

    authors： Crawford RP,Cann CE,Keaveny TM

    更新日期：2003-10-01 00:00:00

  • Local communication on and within bone controls bone remodeling.

    abstract：:Bone remodeling is required for healthy calcium homeostasis and for repair of damage occurring with stress and age. Osteoclasts resorb bone and osteoblasts form bone. These processes normally occur in a tightly regulated sequence of events, where the amount of formed bone equals the amount of resorbed bone, thereby re...

    journal_title：Bone

    pub_type： 杂志文章,评审

    doi：10.1016/j.bone.2009.03.671

    authors： Henriksen K,Neutzsky-Wulff AV,Bonewald LF,Karsdal MA

    更新日期：2009-06-01 00:00:00

  • Age-related changes in trabecular bone microdamage initiation.

    abstract：:With age, alterations occurring in bone quality, quantity, and microarchitecture affect the resistance of trabecular bone to local failure. The clinical implications of these changes are evident by the observed exponential increase in fracture incidence with age. Although age-related development of skeletal fragility ...

    journal_title：Bone

    pub_type： 杂志文章

    doi：10.1016/j.bone.2006.10.028

    authors： Nagaraja S,Lin AS,Guldberg RE

    更新日期：2007-04-01 00:00:00

  • Activated c-Fms recruits Vav and Rac during CSF-1-induced cytoskeletal remodeling and spreading in osteoclasts.

    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

    authors： Sakai H,Chen Y,Itokawa T,Yu KP,Zhu ML,Insogna K

    更新日期：2006-12-01 00:00:00

  • Binding and antiresorptive properties of heterocycle-containing bisphosphonate analogs: structure-activity relationships.

    abstract：:To define structure-activity relationships for bisphosphonate activity, we examined the bone binding and antiresorptive properties of heterocycle-containing analogs of risedronate, a pyridylbisphosphonate, in cultures of mouse fetal bone explants. Our studies indicated that hydroxybisphosphonates with the nitrogen mol...

    journal_title：Bone

    pub_type： 杂志文章

    doi：10.1016/s8756-3282(98)00120-3

    authors： van Beek ER,Löwik CW,Ebetino FH,Papapoulos SE

    更新日期：1998-11-01 00:00:00

  • Positive effect of low dose vitamin D supplementation on growth of fetal bones: A randomized prospective study.

    abstract：:The effect of vitamin D supplementation on growth of fetal bones during pregnancy is unclear. The aim of this study was to assess the effect of low dose vitamin D supplementation during pregnancy on bony anthropometric aspects of the fetus. In this prospective randomized trial, 140 patients were divided into two equal...

    journal_title：Bone

    pub_type： 杂志文章,随机对照试验

    doi：10.1016/j.bone.2019.02.022

    authors： Vafaei H,Asadi N,Kasraeian M,Shahraki HR,Bazrafshan K,Namazi N

    更新日期：2019-05-01 00:00:00

  • WISE-2005: bed-rest induced changes in bone mineral density in women during 60 days simulated microgravity.

    abstract：:To better understand the effects of prolonged bed-rest in women, 24 healthy women aged 25 to 40 years participated in 60-days of strict 6° head-down tilt bed-rest (WISE-2005). Subjects were assigned to either a control group (CON, n=8) which performed no countermeasure, an exercise group (EXE, n=8) undertaking a combi...

    journal_title：Bone

    pub_type： 杂志文章

    doi：10.1016/j.bone.2011.06.021

    authors： Beller G,Belavý DL,Sun L,Armbrecht G,Alexandre C,Felsenberg D

    更新日期：2011-10-01 00:00:00

  • Severe bone loss and multiple fractures in SCN8A-related epileptic encephalopathy.

    abstract：:Mutations in the SCN8A gene encoding the neuronal voltage-gated sodium channel Nav1.6 are known to be associated with epileptic encephalopathy type 13. We identified a novel de novo SCN8A mutation (p.Phe360Ala, c.1078_1079delTTinsGC, Exon 9) in a 6-year-old girl with epileptic encephalopathy accompanied by severe juve...

    journal_title：Bone

    pub_type： 杂志文章

    doi：10.1016/j.bone.2017.06.025

    authors： Rolvien T,Butscheidt S,Jeschke A,Neu A,Denecke J,Kubisch C,Meisler MH,Pueschel K,Barvencik F,Yorgan T,Oheim R,Schinke T,Amling M

    更新日期：2017-10-01 00:00:00