当前位置： SCI文献检索 > OSTEOARTHRITIS AND CARTILAGE期刊下所有文献 > Identification and pharmacological characterization of a novel inhibitor of autotaxin in rodent models of joint pain.

Identification and pharmacological characterization of a novel inhibitor of autotaxin in rodent models of joint pain.

Abstract：

OBJECTIVE:Autotaxin is a secreted lysophospholipase that mediates the conversion of lysophosphatidyl choline (LPC) to lysophosphatidic acid (LPA), a bioactive lipid mediator. Autotaxin levels in plasma and synovial fluid correlate with disease severity in patients with knee osteoarthritis (OA). The goal of this study was to develop and characterize a novel small molecule inhibitor of autotaxin to inhibit LPA production in vivo and determine its efficacy in animal models of musculoskeletal pain. DESIGN:Compound libraries were screened using an LPC coupled enzyme assay that measures the amount of choline released from LPC by the action of autotaxin. Hits from this assay were tested in a plasma assay to assess inhibition of endogenous plasma autotaxin and subsequently tested for their ability to lower plasma LPA levels upon oral dosing of rats. The best compounds were then tested in animal models of musculoskeletal pain. RESULTS:Compound screening led to the identification of compounds with nanomolar potency for inhibition of autotaxin activity. Studies in rats demonstrated a good correlation between compound exposure levels and a decrease in LPA levels in plasma. The leading molecule (compound-1) resulted in a dose dependent decrease in joint pain in the mono-sodium iodoacetate (MIA) and meniscal tear models and a decrease in bone fracture pain in the osteotomy model in rats. CONCLUSION:We have identified and characterized a novel small molecule inhibitor of autotaxin and demonstrated its efficacy in animal models of musculoskeletal pain. The inhibitor has the potential to serve as an analgesic for human OA and bone fracture.

journal_name

Osteoarthritis Cartilage

journal_title

Osteoarthritis and cartilage

authors

Thirunavukkarasu K,Swearingen CA,Oskins JL,Lin C,Bui HH,Jones SB,Pfeifer LA,Norman BH,Mitchell PG,Chambers MG

doi

10.1016/j.joca.2016.09.006

subject

Has Abstract

pub_date

2017-06-01 00:00:00

pages

935-942

issue

6

eissn

1063-4584

issn

1522-9653

pii

S1063-4584(16)30280-1

journal_volume

25

pub_type

杂志文章

相关文献

OSTEOARTHRITIS AND CARTILAGE文献大全
  • Reliability, reproducibility and variability of the traditional Histologic/Histochemical Grading System vs the new OARSI Osteoarthritis Cartilage Histopathology Assessment System.

    abstract：OBJECTIVE:For many years, the Histologic/Histochemical Grading System (HHGS) for osteoarthritis monitoring has been used as a histological scoring system for the quality of cartilage. There are, however, some limitations using this grading system. The goal of the investigation presented in this paper was to examine the...

    journal_title：Osteoarthritis and cartilage

    pub_type： 杂志文章

    doi：10.1016/j.joca.2007.04.017

    authors： Custers RJ,Creemers LB,Verbout AJ,van Rijen MH,Dhert WJ,Saris DB

    更新日期：2007-11-01 00:00:00

  • Expression of vitamin D receptors and matrix metalloproteinases in osteoarthritic cartilage and human articular chondrocytes in vitro.

    abstract：OBJECTIVES:To examine the in situ distributions of vitamin D receptors (VDR) and matrix metalloproteinases (MMPs) in osteoarthritic cartilage for comparison with non-arthritic, normal cartilage; and to assess the in vitro effects of 1alpha,25 dihydroxyvitaminD(3)(1alpha,25(OH)(2)D(3)) on MMPs-1, -3 and -9 and prostagla...

    journal_title：Osteoarthritis and cartilage

    pub_type： 杂志文章

    doi：10.1053/joca.2000.0408

    authors： Tetlow LC,Woolley DE

    更新日期：2001-07-01 00:00:00

  • Chondroitin sulfate and/or glucosamine hydrochloride for Kashin-Beck disease: a cluster-randomized, placebo-controlled study.

    abstract：OBJECTIVE:To evaluate the efficacy and safety of chondroitin sulfate and/or glucosamine hydrochloride in alleviating symptoms and improving the dysfunction of Kashin-Beck disease (KBD) patients. METHODS:We undertook a cluster-randomized, placebo-controlled trial in 251 patients with KBD. Participants were randomly all...

    journal_title：Osteoarthritis and cartilage

    pub_type： 杂志文章,随机对照试验

    doi：10.1016/j.joca.2012.03.013

    authors： Yue J,Yang M,Yi S,Dong B,Li W,Yang Z,Lu J,Zhang R,Yong J

    更新日期：2012-07-01 00:00:00

  • Dicam promotes proliferation and maturation of chondrocyte through Indian hedgehog signaling in primary cilia.

    abstract：OBJECTIVES:Primary cilium is required for mechano-biological signal transduction in chondrocytes, and its interaction with extracellular matrix is critical for cartilage homeostasis. However, the role of cilia-associated proteins that affect the function of cilia remains to be elucidated. Here, we show that Dicam has a...

    journal_title：Osteoarthritis and cartilage

    pub_type： 杂志文章

    doi：10.1016/j.joca.2018.04.008

    authors： Han S,Park HR,Lee EJ,Jang JA,Han MS,Kim GW,Jeong JH,Choi JY,Beier F,Jung YK

    更新日期：2018-07-01 00:00:00

  • Epigenetically mediated spontaneous reduction of NFAT1 expression causes imbalanced metabolic activities of articular chondrocytes in aged mice.

    abstract：OBJECTIVE:Abnormal metabolic activities of chondrocytes may cause articular cartilage (AC) degradation, but key transcription factors regulating metabolic activities in AC of aging individuals remain unknown. This study aimed to investigate the role of transcription factor NFAT1 in regulating the expression of anabolic...

    journal_title：Osteoarthritis and cartilage

    pub_type： 杂志文章

    doi：10.1016/j.joca.2016.02.003

    authors： Zhang M,Lu Q,Egan B,Zhong XB,Brandt K,Wang J

    更新日期：2016-07-01 00:00:00

  • Mechanical symptoms as an indication for knee arthroscopy in patients with degenerative meniscus tear: a prospective cohort study.

    abstract：OBJECTIVE:According to prevailing consensus, patients with mechanical symptoms are those considered to most likely benefit from arthroscopic surgery. The aim of this study was to determine the value of using patients' pre-operative self-reports of mechanical symptoms as a justification surgery in patients with degenera...

    journal_title：Osteoarthritis and cartilage

    pub_type： 杂志文章

    doi：10.1016/j.joca.2016.03.013

    authors： Sihvonen R,Englund M,Turkiewicz A,Järvinen TL

    更新日期：2016-08-01 00:00:00

  • Varus thrust during walking and the risk of incident and worsening medial tibiofemoral MRI lesions: the Multicenter Osteoarthritis Study.

    abstract：OBJECTIVE:To determine the association of varus thrust during walking to incident and worsening medial tibiofemoral cartilage damage and bone marrow lesions (BMLs) over 2 years in older adults with or at risk for osteoarthritis (OA). METHOD:Subjects from the Multicenter Osteoarthritis Study (MOST) were studied. Varus ...

    journal_title：Osteoarthritis and cartilage

    pub_type： 杂志文章,多中心研究

    doi：10.1016/j.joca.2017.01.005

    authors： Wink AE,Gross KD,Brown CA,Guermazi A,Roemer F,Niu J,Torner J,Lewis CE,Nevitt MC,Tolstykh I,Sharma L,Felson DT

    更新日期：2017-06-01 00:00:00

  • Cartilage growth and remodeling: modulation of balance between proteoglycan and collagen network in vitro with beta-aminopropionitrile.

    abstract：OBJECTIVE:To examine the effect of beta-aminopropionitrile (BAPN), an inhibitor of lysyl oxidase, on growth and remodeling of immature articular cartilage in vitro. DESIGN:Immature bovine articular cartilage explants from the superficial and middle layers were cultured for 13 days in serum-containing medium with or wi...

    journal_title：Osteoarthritis and cartilage

    pub_type： 杂志文章

    doi：10.1016/j.joca.2007.05.019

    authors： Asanbaeva A,Masuda K,Thonar EJ,Klisch SM,Sah RL

    更新日期：2008-01-01 00:00:00

  • Validation of high-resolution water-excitation magnetic resonance imaging for quantitative assessment of thin cartilage layers.

    abstract：OBJECTIVE:To employ a magnetic resonance (MR) imaging technique for quantitative assessment of thin cartilage layers, and to validate the cartilage volume and thickness measurements. METHODS:We investigated 10 normal elbow joints (age 20 to 69 years) with a 3D gradient echo sequence with selective water excitation (TR...

    journal_title：Osteoarthritis and cartilage

    pub_type： 杂志文章

    doi：10.1053/joca.1999.0278

    authors： Graichen H,Springer V,Flaman T,Stammberger T,Glaser C,Englmeier KH,Reiser M,Eckstein F

    更新日期：2000-03-01 00:00:00

  • Evidence for functional ATP-sensitive (K(ATP)) potassium channels in human and equine articular chondrocytes.

    abstract：OBJECTIVE:Chondrocytes are highly sensitive to variations in extracellular glucose and oxygen levels in the extracellular matrix. As such, they must possess a number of mechanisms to detect and respond to alterations in the metabolic state of cartilage. In other organs such as the pancreas, heart and brain, such detect...

    journal_title：Osteoarthritis and cartilage

    pub_type： 杂志文章

    doi：10.1016/j.joca.2006.06.017

    authors： Mobasheri A,Gent TC,Nash AI,Womack MD,Moskaluk CA,Barrett-Jolley R

    更新日期：2007-01-01 00:00:00

  • Tumor risk by tissue engineering: cartilaginous differentiation of mesenchymal stem cells reduces tumor growth.

    abstract：OBJECTIVE:Implantation of autologous chondrocytes (AC) is a promising option for the treatment of cartilage defects, but problems with cell harvesting, dedifferentiation, or the donor age limit the clinical outcome. Mesenchymal stem cells (MSC) gain much interest because of their simple isolation and multipotential dif...

    journal_title：Osteoarthritis and cartilage

    pub_type： 杂志文章

    doi：10.1016/j.joca.2009.10.015

    authors： Akay I,Oxmann D,Helfenstein A,Mentlein R,Schünke M,Hassenpflug J,Kurz B

    更新日期：2010-03-01 00:00:00

  • Radiographic assessment of osteoarthritis: comparison between existing methodologies.

    abstract：:Radiographic sensitivity for quantifying the rate of change in joint space width (JSW) for DMOAD trials, is influenced by the following, which vary between methodologies for imaging hip, knee and hand. Radio-anatomical plane of measurement JSW measurement precision is improve when the (i) joint is in a normal function...

    journal_title：Osteoarthritis and cartilage

    pub_type： 杂志文章,评审

    doi：10.1053/joca.1998.0234

    authors： Buckland-Wright

    更新日期：1999-07-01 00:00:00

  • Long-term clinical and economic outcomes of a short-term physical activity program in knee osteoarthritis patients.

    abstract：OBJECTIVE:Physical activity (PA) in the US knee osteoarthritis (OA) population is low, despite well-established health benefits. PA program implementation is often stymied by sustainability concerns. We sought to establish parameters that would make a short-term (3-year efficacy) PA program a cost-effective component o...

    journal_title：Osteoarthritis and cartilage

    pub_type： 杂志文章

    doi：10.1016/j.joca.2020.01.017

    authors： Silva GS,Sullivan JK,Katz JN,Messier SP,Hunter DJ,Losina E

    更新日期：2020-06-01 00:00:00

  • The innate immune response as a mediator of osteoarthritis pain.

    abstract：:In this narrative review, we discuss the emerging role of innate immunity in osteoarthritis (OA) joint pain. First, we give a brief description of the pain pathway in the context of OA. Then we consider how neuro-immune signaling pathways may promote OA pain. First, activation of neuronal Pattern Recognition Receptors...

    journal_title：Osteoarthritis and cartilage

    pub_type： 杂志文章,评审

    doi：10.1016/j.joca.2019.11.006

    authors： Miller RJ,Malfait AM,Miller RE

    更新日期：2020-05-01 00:00:00

  • Estrogen reduces mechanical injury-related cell death and proteoglycan degradation in mature articular cartilage independent of the presence of the superficial zone tissue.

    abstract：OBJECTIVE:To study the effect of 17β-estradiol (E2) and the superficial zone (SFZ) on cell death and proteoglycan degradation in articular cartilage after a single injurious compression in vitro. METHOD:Cartilage explants from the femoropatellar groove of 2 year old cows with or without the SFZ were cultured serum-fre...

    journal_title：Osteoarthritis and cartilage

    pub_type： 杂志文章

    doi：10.1016/j.joca.2013.07.007

    authors： Imgenberg J,Rolauffs B,Grodzinsky AJ,Schünke M,Kurz B

    更新日期：2013-11-01 00:00:00

  • Stimulating effect of diacerein on TGF-beta1 and beta2 expression in articular chondrocytes cultured with and without interleukin-1.

    abstract：OBJECTIVE:Diacetylrhein or diacerein has shown efficacy in the treatment of both major forms of osteoarthritis (OA), coxarthrosis as well as gonarthrosis, improving clinical symptoms of the disease (pain reduction and algo-functional index). Both in-vitro and animal models studies suggest that diacerein may have also d...

    journal_title：Osteoarthritis and cartilage

    pub_type： 杂志文章

    doi：10.1053/joca.1998.0199

    authors： Felisaz N,Boumediene K,Ghayor C,Herrouin JF,Bogdanowicz P,Galerra P,Pujol JP

    更新日期：1999-05-01 00:00:00

  • Occupational risk factors for osteoarthritis of the knee: a meta-analysis.

    abstract：INTRODUCTION:Systematic reviews agree that knee osteoarthritis (OA) is related to occupational activities, but have not quantified the overall risks. METHODS:Systematic review of observational studies of knee OA and occupation. Job titles, elite sport, heavy work, kneeling, and other activities were included. Relative...

    journal_title：Osteoarthritis and cartilage

    pub_type： 杂志文章,meta分析,评审

    doi：10.1016/j.joca.2011.02.016

    authors： McWilliams DF,Leeb BF,Muthuri SG,Doherty M,Zhang W

    更新日期：2011-07-01 00:00:00

  • Radiographic hand osteoarthritis: patterns and associations with hand pain and function in a community-dwelling sample.

    abstract：OBJECTIVE:Patterns of radiographic osteoarthritis (ROA) of the hand are often examined by row, with the four joints of the thumb studied inconsistently. The objectives of this study were to determine relationships of ROA at different hand joints, use the findings to define radiographic sub-groups and investigate their ...

    journal_title：Osteoarthritis and cartilage

    pub_type： 杂志文章

    doi：10.1016/j.joca.2009.05.009

    authors： Marshall M,van der Windt D,Nicholls E,Myers H,Hay E,Dziedzic K

    更新日期：2009-11-01 00:00:00

  • Modeling and predicting osteoarthritis progression: data from the osteoarthritis initiative.

    abstract：OBJECTIVE:The goal of this study was to model the longitudinal progression of knee osteoarthritis (OA) and build a prognostic tool that uses data collected in 1 year to predict disease progression over 8 years. DESIGN:To model OA progression, we used a mixed-effects mixture model and 8-year data from the Osteoarthriti...

    journal_title：Osteoarthritis and cartilage

    pub_type： 杂志文章

    doi：10.1016/j.joca.2018.08.003

    authors： Halilaj E,Le Y,Hicks JL,Hastie TJ,Delp SL

    更新日期：2018-12-01 00:00:00

  • Clinical feasibility of a novel biphasic osteochondral composite for matrix-associated autologous chondrocyte implantation.

    abstract：OBJECTIVE:Matrix-associated autologous chondrocyte implantation has been used to treat cartilage defects. We developed a biphasic cylindrical osteochondral composite construct for such use, and conducted this study to determine its feasibility for treating osteochondral lesions in human knees. METHOD:Ten patients with...

    journal_title：Osteoarthritis and cartilage

    pub_type： 杂志文章

    doi：10.1016/j.joca.2013.01.004

    authors： Chiang H,Liao CJ,Hsieh CH,Shen CY,Huang YY,Jiang CC

    更新日期：2013-04-01 00:00:00

  • NEL-like molecule-1-modified bone marrow mesenchymal stem cells/poly lactic-co-glycolic acid composite improves repair of large osteochondral defects in mandibular condyle.

    abstract：OBJECTIVE:Articular cartilage of the mandibular condyle has limited ability to regenerate itself after injury. This study was to investigate whether osteochondral defects in mandibular condyle could be repaired by NELL-1(NEL-like molecule-1)-modified autogenous bone marrow mesenchymal stem cells (BMMSCs) and poly lacti...

    journal_title：Osteoarthritis and cartilage

    pub_type： 杂志文章

    doi：10.1016/j.joca.2011.02.015

    authors： Zhu S,Zhang B,Man C,Ma Y,Hu J

    更新日期：2011-06-01 00:00:00

  • C-reactive protein, metabolic syndrome and incidence of severe hip and knee osteoarthritis. A population-based cohort study.

    abstract：OBJECTIVE:To explore the relationships between C-reactive protein (CRP), metabolic syndrome (MetS) and incidence of severe knee or hip osteoarthritis (OA) in a prospective study. METHODS:A population-based cohort (n=5171, mean age 57.5+/-5.9 years) was examined between 1991 and 1994. Data was collected on lifestyle ha...

    journal_title：Osteoarthritis and cartilage

    pub_type： 杂志文章

    doi：10.1016/j.joca.2008.07.003

    authors： Engström G,Gerhardsson de Verdier M,Rollof J,Nilsson PM,Lohmander LS

    更新日期：2009-02-01 00:00:00

  • Detection of changes in cartilage water content using MRI T2-mapping in vivo.

    abstract：OBJECTIVES:Osteoarthritis (OA) is the most prevalent chronic disease in the elderly, and it is generally diagnosed at an advanced state when treatment is difficult if not impossible. The early form of OA is characterized by an elevated water content in the cartilage tissue. The purpose of this study was to verify in vi...

    journal_title：Osteoarthritis and cartilage

    pub_type： 杂志文章

    doi：10.1053/joca.2002.0847

    authors： Liess C,Lüsse S,Karger N,Heller M,Glüer CC

    更新日期：2002-12-01 00:00:00

  • REMOVED: Generation of cartilage microtissues by hanging drops: effect of different culture conditions.

    abstract：:This article has been removed, consistent with Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). The Publisher apologizes for any inconvenience this may cause. ...

    journal_title：Osteoarthritis and cartilage

    pub_type： 杂志文章

    doi：10.1016/j.joca.2007.03.002

    authors： Martinez I

    更新日期：2007-04-27 00:00:00

  • Human articular chondrocytes with higher aldehyde dehydrogenase activity have stronger expression of COL2A1 and SOX9.

    abstract：OBJECTIVE:To determine in human articular chondrocytes the activity of Aldehyde dehydrogenase (ALDH), which are reported as stem/progenitor cell marker in various adult tissues and evaluate gene expression of ALDH1A isoforms. DESIGN:ALDH activity was evaluated by flow cytometry with Aldefluor™ assay in cells, isolated...

    journal_title：Osteoarthritis and cartilage

    pub_type： 杂志文章

    doi：10.1016/j.joca.2015.11.019

    authors： Unguryte A,Bernotiene E,Bagdonas E,Garberyte S,Porvaneckas N,Jorgensen C

    更新日期：2016-05-01 00:00:00

  • The association between patella alignment and knee pain and function: an MRI study in persons with symptomatic knee osteoarthritis.

    abstract：OBJECTIVE:The aim of the study was to examine the association between patellofemoral (PF) alignment (using standard magnetic resonance imaging (MRI) images of extended knees) and knee pain and function. DESIGN:Subjects were recruited to participate in a natural history study of symptomatic knee osteoarthritis, called ...

    journal_title：Osteoarthritis and cartilage

    pub_type： 杂志文章

    doi：10.1016/j.joca.2007.04.014

    authors： Kalichman L,Zhu Y,Zhang Y,Niu J,Gale D,Felson DT,Hunter D

    更新日期：2007-11-01 00:00:00

  • A meta-analysis of sex differences prevalence, incidence and severity of osteoarthritis.

    abstract：OBJECTIVE:To resolve uncertainty regarding sex differences in osteoarthritis (OA) by performing a meta-analysis of sex differences in OA prevalence, incidence and severity. METHODS:Standard search strategies for population-based studies of OA providing sex-specific data. Random effects meta-analysis to provide pooled ...

    journal_title：Osteoarthritis and cartilage

    pub_type： 杂志文章,meta分析

    doi：10.1016/j.joca.2005.04.014

    authors： Srikanth VK,Fryer JL,Zhai G,Winzenberg TM,Hosmer D,Jones G

    更新日期：2005-09-01 00:00:00

  • Methodologic issues in clinical trials for prevention or risk reduction in osteoarthritis.

    abstract：:The design and execution of prevention trials for OA have methodological issues that are distinct from trials designed to impact prevalent disease. Disease definitions and their precise and sensitive measurement, identification of high-risk populations, the nature of the intervention (pharmaceutical, nutraceutical, be...

    journal_title：Osteoarthritis and cartilage

    pub_type： 共识发展会议,杂志文章

    doi：10.1016/j.joca.2010.10.031

    authors： Jordan JM,Sowers MF,Messier SP,Bradley J,Arangio G,Katz JN,Losina E,Rovati L,Bachtell N,Cooper C,Spector T,Zhang W,Gardiner J,Wahba M

    更新日期：2011-05-01 00:00:00

  • Localized 3D analysis of cartilage composition and morphology in small animal models of joint degeneration.

    abstract：OBJECTIVE:Current histological scoring methods to evaluate efficacy of potential therapeutics for slowing or preventing joint degeneration are time-consuming and semi-quantitative in nature. Hence, there is a need to develop and standardize quantitative outcome measures to define sensitive metrics for studying potentia...

    journal_title：Osteoarthritis and cartilage

    pub_type： 杂志文章

    doi：10.1016/j.joca.2013.05.018

    authors： Thote T,Lin AS,Raji Y,Moran S,Stevens HY,Hart M,Kamath RV,Guldberg RE,Willett NJ

    更新日期：2013-08-01 00:00:00

  • Natural history of cartilage damage and osteoarthritis progression on magnetic resonance imaging in a population-based cohort with knee pain.

    abstract：OBJECTIVES:To determine the natural history of cartilage damage and of osteoarthritis (OA) progression using magnetic resonance imaging (MRI); to evaluate whether OA progression varies by stage of disease. METHODS:A population-based cohort with knee pain was assessed clinically, with X-ray (Kellgren-Lawrence [KL] grad...

    journal_title：Osteoarthritis and cartilage

    pub_type： 杂志文章

    doi：10.1016/j.joca.2011.02.008

    authors： Cibere J,Sayre EC,Guermazi A,Nicolaou S,Kopec JA,Esdaile JM,Thorne A,Singer J,Wong H

    更新日期：2011-06-01 00:00:00