Abstract：
:Tankyrase is a poly (ADP-ribose) polymerase that leads to ubiquitination and degradation of target proteins. Since tankyrase inhibitors suppress the degradation of AXIN protein, a negative regulator of the canonical Wnt pathway, they effectively act as Wnt inhibitors. Small molecule tankyrase inhibitors are being investigated as drug candidates for cancer and fibrotic diseases, in which the Wnt pathways are aberrantly activated. Tankyrase is also reported to degrade the adaptor protein SH3BP2 (SH3 domain-binding protein 2). We have previously shown that SH3BP2 gain-of-function mutation enhances receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis in murine bone marrow-derived macrophages (BMMs). Although the interaction between tankyrase and SH3BP2 has been reported, it is not clear whether and how the inhibition of tankyrase affects bone cells and bone mass. Here, we have demonstrated that tankyrase inhibitors (IWR-1, XAV939, and G007-LK) enhanced RANKL-induced osteoclast formation and function in murine BMMs and human peripheral blood mononuclear cells through the accumulation of SH3BP2, subsequent phosphorylation of SYK, and nuclear translocation of NFATc1. Tankyrase inhibitors also enhanced osteoblast differentiation and maturation, represented by increased expression of osteoblast-associated genes accompanied by the accumulation of SH3BP2 protein and enhanced nuclear translocation of ABL, TAZ, and Runx2 in primary osteoblasts. Most importantly, pharmacological inhibition of tankyrase in mice significantly decreased tibia and lumbar vertebrae bone volumes in association with increased numbers of osteoclasts. Our findings uncover the role of tankyrase inhibition in bone cells and highlight the potential adverse effects of the inhibitor on bone.
journal_name
Bonejournal_title
Boneauthors
Fujita S,Mukai T,Mito T,Kodama S,Nagasu A,Kittaka M,Sone T,Ueki Y,Morita Ydoi
10.1016/j.bone.2017.10.017subject
Has Abstractpub_date
2018-01-01 00:00:00pages
156-166eissn
8756-3282issn
1873-2763pii
S8756-3282(17)30383-6journal_volume
106pub_type
杂志文章相关文献
BONE文献大全abstract：:Controversial results were reported on the association of vitamin D receptor (VDR) polymorphisms and bone mineral density (BMD). We studied allelic frequencies of the BsmI, ApaI, and TaqI restriction fragment length polymorphisms (RFLPs) in 144 normal healthy southern Chinese premenopausal women aged between 30 and 40...
journal_title：Bone
pub_type： 杂志文章
doi：10.1016/s8756-3282(97)00301-3
更新日期：1998-04-01 00:00:00
abstract：:Understanding the cellular basis of osteoblastic cell-biomaterial interaction is crucial to the analysis of the mechanism of osseointegration, a requirement of long-term orthopedic implant stability. Clinically, the amount of bone ingrowth is variable, and cellular parameters that influence ingrowth have yet to be cle...
journal_title：Bone
pub_type： 杂志文章
doi：10.1016/s8756-3282(99)00077-0
更新日期：1999-05-01 00:00:00
abstract：:Spinal cord injury (SCI) results in a dramatic loss of bone mineral and a marked increase in fracture incidence in the femur; however, its effect on the femur's geometric structure and strength is poorly studied. The primary purpose of the present study was to assess the geometric structure, composition, and strength ...
journal_title：Bone
pub_type： 杂志文章
doi：10.1016/j.bone.2004.10.012
更新日期：2005-02-01 00:00:00
abstract：:Hypophosphatasia (HPP) is a multi-systemic inborn disease with an extraordinary spectrum of severity, ranging from the absence of mineralization to high lethality and it involves different organs including bone, muscle, kidney, lung, gastrointestinal tract and the nervous system. The disease is characterized by low le...
journal_title：Bone
pub_type： 杂志文章
doi：10.1016/j.bone.2016.10.022
更新日期：2017-01-01 00:00:00
abstract：BACKGROUND:High-resolution peripheral quantitative computed tomography (HR-pQCT) represents a three-dimensional tool for the screening of osteoporosis patients i.e., regarding fracture risk. The purpose of this study was to determine the baseline and follow-up bone microarchitecture in relation to incident fracture ris...
journal_title：Bone
pub_type： 杂志文章
doi：10.1016/j.bone.2018.06.022
更新日期：2018-09-01 00:00:00
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
更新日期：2003-10-01 00:00:00
abstract：:We believe that the assembled data are consistent with the presence of mRNA species and/or proteins in pagetic bone that are recognized by some paramyxovirus antibodies and nucleic acid probes. The evidence presented so far is insufficient to substantiate claims for the "unequivocal" presence of paramyxovirus sequence...
journal_title：Bone
pub_type： 杂志文章,评审
doi：10.1016/s8756-3282(99)00032-0
更新日期：1999-05-01 00:00:00
abstract：:We have tested the ability of the XCT960A to detect bone loss in OVX-rats, as well as bone gain in the proximal tibial metaphysis of healthy rats treated with hPTH(1-34). The results demonstrated that high precision can be achieved, with CV's for most measurement parameters in the range of 1.6 to 5.9% being obtained i...
journal_title：Bone
pub_type： 杂志文章
doi：10.1016/8756-3282(95)00287-n
更新日期：1995-10-01 00:00:00
abstract：:In 1994, the World Health Organization published diagnostic criteria for osteoporosis. Since then, many new technologies have been developed for the measurement of bone mineral at multiple skeletal sites. The information provided by each assessment will describe the clinical characteristics, fracture risk and epidemio...
journal_title：Bone
pub_type： 杂志文章,评审
doi：10.1016/j.bone.2007.11.001
更新日期：2008-03-01 00:00:00
abstract：:Osteoimmunological interactions are central to maintaining bone homeostasis and are key mechanisms in bone pathology. Macrophages are highly adaptable cells with pleiotropic actions. They have important roles in development, homeostasis and both innate and adaptive immunity. Macrophages can have broad ranging effects ...
journal_title：Bone
pub_type： 杂志文章,评审
doi：10.1016/j.bone.2008.08.128
更新日期：2008-12-01 00:00:00
abstract：BACKGROUND:X-linked hypophosphatemia (XLH) causes rickets, osteomalacia, skeletal deformities and growth impairment, due to elevated fibroblast growth factor 23 and hypophosphatemia. Conventional therapy requires high doses of phosphate salts combined with active vitamin D analogues. Risks of this regimen include nephr...
journal_title：Bone
pub_type： 杂志文章
doi：10.1016/j.bone.2019.06.025
更新日期：2019-10-01 00:00:00
abstract：:The conventional stereologic procedure for estimating bone surface densities in iliac crest biopsies gives biased estimates because bone substructure is anisotropic and the sectioning of the biopsies is intended to be parallel to the cylindrical axis of the iliac crest biopsy. It has recently been shown that random an...
journal_title：Bone
pub_type： 杂志文章
doi：10.1016/8756-3282(87)90126-8
更新日期：1987-01-01 00:00:00
abstract：:A predictable animal model with skeletal remodeling characteristics similar to those of humans is needed to facilitate the understanding of the mechanism of postmenopausal osteoporosis. We have utilized the ovariohysterectomized (Ovh) dog to examine cellular and biochemical responses to estrogen depletion and PTH stim...
journal_title：Bone
pub_type： 杂志文章
doi：10.1016/8756-3282(92)90075-8
更新日期：1992-01-01 00:00:00
abstract：:The prediction of bone strength can be improved when determining bone mineral density (BMD) in combination with measures of trabecular microarchitecture. The goal of this study was to assess parameters of trabecular bone structure and texture of the calcaneus by clinical multi-detector row computed tomography (MDCT) i...
journal_title：Bone
pub_type： 杂志文章
doi：10.1016/j.bone.2009.01.372
更新日期：2009-05-01 00:00:00
abstract：:Over 60% of our severely combat-injured patient population develops radiographically apparent heterotopic ossification. Nearly a third of these require surgical excision of symptomatic lesions, a procedure that is fraught with complications, and delays or regresses functional rehabilitation in many cases. Unfortunatel...
journal_title：Bone
pub_type： 杂志文章
doi：10.1016/j.bone.2013.08.026
更新日期：2013-12-01 00:00:00
abstract：BACKGROUND AND OBJECTIVES:Chronic kidney disease (CKD) is commonly associated with mineral and bone metabolism disorders, but these are less frequently studied in non-dialysis CKD patients than in dialysis patients. We examined and described international variation in mineral and bone disease (MBD) markers and their tr...
journal_title：Bone
pub_type： 杂志文章
doi：10.1016/j.bone.2019.115058
更新日期：2019-12-01 00:00:00
abstract：:Sclerosteosis and van Buchem disease are two rare bone sclerosing dysplasias caused by genetic defects in the synthesis of sclerostin. In this article we review the demographic, clinical, biochemical, radiological, and histological characteristics of patients with sclerosteosis and van Buchem disease that led to a bet...
journal_title：Bone
pub_type： 杂志文章,评审
doi：10.1016/j.bone.2016.10.010
更新日期：2017-03-01 00:00:00
abstract：:Bone matrix, mainly composed of type I collagen and apatite, is constantly modified during the bone remodeling process, which exposes bone cells to various proportions of mineralized collagen within bone structural units. Collagen-mineralized substrates have been shown to increase osteoblast activities. We hypothesize...
journal_title：Bone
pub_type： 杂志文章
doi：10.1016/j.bone.2010.03.010
更新日期：2010-07-01 00:00:00
abstract：:Bone geometry plays a prominent role in bone strength. Cross-sectional studies have shown that advancing age is associated with increasing diameter of long bones, related to both periostal apposition and endosteal resorption. However, there are few data provided by prospective studies, especially concerning the change...
journal_title：Bone
pub_type： 杂志文章
doi：10.1016/j.bone.2010.03.020
更新日期：2010-08-01 00:00:00
abstract：:Low body weight is associated with an increased risk for osteoporosis and fractures, but the contribution of other lifestyle related factors have not been previously studied within lean elderly women. The present study evaluated the association between lifelong lifestyle factors and bone density, falls and postmenopau...
journal_title：Bone
pub_type： 杂志文章
doi：10.1016/j.bone.2006.01.143
更新日期：2006-08-01 00:00:00
abstract：UNLABELLED:We identified regions inside the proximal femur that are most strongly associated with hip fracture. Bone densitometry based on such fracture-critical regions showed improved power in discriminating fracture patients from controls. INTRODUCTION:Hip fractures typically occur in lateral falls, with focal mech...
journal_title：Bone
pub_type： 杂志文章
doi：10.1016/j.bone.2008.12.008
更新日期：2009-04-01 00:00:00
abstract：:Insulin-dependent type 1 diabetes mellitus (IDDM) has been shown to alter the properties of bone and impair bone repair in both humans and animals. The objective of this study was the detailed histomorphometric evaluation of the influence of the diabetic metabolic state on bone formation and remodeling during bone def...
journal_title：Bone
pub_type： 杂志文章
doi：10.1016/j.bone.2004.03.011
更新日期：2004-07-01 00:00:00
abstract：:Ultrashort echo time magnetic resonance imaging (UTE-MRI) techniques have been increasingly used to assess cortical bone microstructure. High resolution micro computed tomography (μCT) is routinely employed for validating the MRI-based assessments. However, water protons in cortical bone may reside in micropores small...
journal_title：Bone
pub_type： 杂志文章
doi：10.1016/j.bone.2019.03.013
更新日期：2019-06-01 00:00:00
abstract：INTRODUCTION:Studies on the association of vitamin D and bone mineral density (BMD) in adolescence and young adults have shown contrasting results. None of these studies have examined the course and baseline in vitamin D intake. The purpose of this study was to examine the association between baseline and the course of...
journal_title：Bone
pub_type： 杂志文章
doi：10.1016/j.bone.2008.10.055
更新日期：2009-03-01 00:00:00
abstract：:The objective was to quantify the outcome of osteoporosis (OP) in terms of health-related quality of life (HR-QOL) and cost of ambulatory care and to look at the association between these two outcomes variables. A cross-sectional health survey of 4800 Belgian individuals over the age of 45 years was used. Individuals ...
journal_title：Bone
pub_type： 杂志文章
doi：10.1016/s8756-3282(03)00089-9
更新日期：2003-06-01 00:00:00
abstract：:Although it is generally acknowledged that matrix vesicles and alkaline phosphatase are required for cartilage calcification, their precise role in initiation or propagation of mineralization remains controversial. We have investigated this problem in a neoplastic model of chondrogenesis, the Swarm rat chondrosarcoma....
journal_title：Bone
pub_type： 杂志文章
doi：10.1016/8756-3282(88)90036-1
更新日期：1988-01-01 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：:Sclerostin, product of the SOST gene, is an important determinant of bone formation and resorption. Adolescents with anorexia nervosa (AN) have low bone density and decreased levels of bone turnover markers. However, sclerostin has not been examined in AN as a potential mediator of impaired bone metabolism. Our study ...
journal_title：Bone
pub_type： 杂志文章,随机对照试验
doi：10.1016/j.bone.2012.06.006
更新日期：2012-09-01 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：:Prenatal dexamethasone exposure (PDE) induces developmental toxicities of multi-organs and susceptibility to multi-diseases in offspring. However, the effects of PDE on osteoarthritis susceptibility in adult offspring and its mechanism have not been reported. In the present study, we treated pregnant Wistar rats with ...
journal_title：Bone
pub_type： 杂志文章
doi：10.1016/j.bone.2020.115245
更新日期：2020-04-01 00:00:00
