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 and catabolic molecules in AC of aged mice. METHODS:The hip, knee, and shoulder joints of BALB/c mice were harvested at 6, 12, 15, 18, and 24 months of age for histopathological and immunohistochemical (IHC) analyses. Total RNA was isolated from AC for gene expression. Genomic DNA and chromatin were prepared from AC for methylated DNA immunoprecipitation (MeDIP) and chromatin immunoprecipitation (ChIP) assays. RESULTS:NFAT1 expression in AC of mice was significantly decreased after 12 months of age, which was associated with reduced proteoglycan staining, decreased expression of chondrocyte markers, and increased expression of interleukin-1β. Forced Nfat1 expression in chondrocytes from aged mice significantly reversed the abnormal metabolic activities. ChIP assays confirmed that NFAT1 bound to the promoter of the Acan, Col2a1, Col9a1, Col11a1, Il1b, Mmp13 and Tnfa genes in articular chondrocytes of aged mice. ChIP and MeDIP assays revealed that reduced NFAT1 expression in AC of aged mice was regulated by epigenetic histone methylation at the promoter region and was correlated with increased DNA methylation at introns 1 and 10 of the Nfat1 gene. CONCLUSION:NFAT1 is a transcriptional regulator of multiple anabolic and catabolic genes in AC of aged mice. Epigenetically mediated reduction of NFAT1 expression causes imbalanced metabolic activities of articular chondrocytes in aged mice.

authors

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

doi

10.1016/j.joca.2016.02.003

subject

Has Abstract

pub_date

2016-07-01 00:00:00

pages

1274-83

issue

7

eissn

1063-4584

issn

1522-9653

pii

S1063-4584(16)01024-4

journal_volume

24

pub_type

杂志文章
  • Cartilage loss in radiographically normal knees depends on radiographic status of the contralateral knee - data from the Osteoarthritis Initiative.

    abstract:OBJECTIVE:To test whether radiographically normal knees with contralateral radiographic knee osteoarthritis (OA), but without contralateral trauma history, display greater cartilage thickness loss than knees from subjects with bilaterally radiographically normal knees. METHODS:828 radiographically normal knees (Kellgr...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章

    doi:10.1016/j.joca.2018.10.006

    authors: Eckstein F,Maschek S,Roemer FW,Duda GN,Sharma L,Wirth W

    更新日期:2019-02-01 00:00:00

  • The efficacy, safety and carry-over effect of diacerein in the treatment of painful knee osteoarthritis: a randomised, double-blind, NSAID-controlled study.

    abstract:OBJECTIVE:To evaluate the efficacy, safety and carry-over effect of diacerein, in comparison to piroxicam, in the treatment of Thai patients with symptomatic knee osteoarthritis (OA). DESIGN:This was a double-blind, randomised, piroxicam-controlled, parallel-group study. A 7-day non-steroidal anti-inflammatory drug wa...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章,随机对照试验

    doi:10.1016/j.joca.2007.02.021

    authors: Louthrenoo W,Nilganuwong S,Aksaranugraha S,Asavatanabodee P,Saengnipanthkul S,Thai Study Group.

    更新日期:2007-06-01 00:00:00

  • Osteoarthritis and the incidence of fracture in the United Kingdom: a retrospective cohort study of 258,696 patients.

    abstract:OBJECTIVE:The goal of this study was to analyze the relationship between osteoarthritis and the incidence of fracture in men and women aged ≥18 years followed in general practices in the United Kingdom. METHODS:This study included patients aged ≥18 years who had received an initial diagnosis of osteoarthritis in one o...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章

    doi:10.1016/j.joca.2020.12.006

    authors: Jacob L,Kostev K

    更新日期:2020-12-21 00:00:00

  • First insights into human acetabular labrum cell metabolism.

    abstract:OBJECTIVE:Hip labrum pathology has only begun to emerge as a significant source of groin pain in the last decade since the development of hip arthroscopy. Few data are available on the anatomy, histology and function of this structure. Moreover, no metabolic data exist at cellular level. The aim of this study was to ch...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章

    doi:10.1016/j.joca.2012.03.023

    authors: Dhollander AA,Lambrecht S,Verdonk PC,Audenaert EA,Almqvist KF,Pattyn C,Verdonk R,Elewaut D,Verbruggen G

    更新日期:2012-07-01 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

  • ADAMTS and ADAM metalloproteinases in osteoarthritis - looking beyond the 'usual suspects'.

    abstract:INTRODUCTION:Matrix metalloproteinases (MMPs) and 'aggrecanase' a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs) are well established to play key roles in osteoarthritis (OA) through degradation of extracellular matrix (ECM) type II collagen and aggrecan, and are thus potential targets for devel...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章,评审

    doi:10.1016/j.joca.2017.02.791

    authors: Yang CY,Chanalaris A,Troeberg L

    更新日期:2017-07-01 00:00:00

  • Nondestructive assessment of sGAG content and distribution in normal and degraded rat articular cartilage via EPIC-microCT.

    abstract:OBJECTIVE:The objective of this study was to evaluate the feasibility of quantifying the Equilibrium Partitioning of an Ionic Contrast agent via Microcomputed Tomography (EPIC-microCT) to nondestructively assess sulfated glycosaminoglycan (sGAG) content and distribution in rat articular cartilage ex vivo, and in doing ...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章

    doi:10.1016/j.joca.2009.07.014

    authors: Xie L,Lin AS,Guldberg RE,Levenston ME

    更新日期:2010-01-01 00:00:00

  • Measurement properties of the WOMAC LK 3.1 pain scale.

    abstract:OBJECTIVE:The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) is applied extensively to patients with osteoarthritis of the hip or knee. Previous work has challenged the validity of its physical function scale however an extensive evaluation of its pain scale has not been reported. Our purpose wa...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章

    doi:10.1016/j.joca.2006.09.005

    authors: Stratford PW,Kennedy DM,Woodhouse LJ,Spadoni GF

    更新日期:2007-03-01 00:00:00

  • Standing balance post total knee arthroplasty: sensitivity to change analysis from four to twelve weeks in 466 patients.

    abstract:OBJECTIVE:Little is known about how static standing balance changes post total knee arthroplasty (TKA). The primary aim of this study was to examine the sensitivity to change and redundancy of center of pressure (COP) variables post-TKA. The secondary aim was to compare the sensitivity of these measures to standard cli...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章

    doi:10.1016/j.joca.2016.08.009

    authors: Clark RA,Seah FJ,Chong HC,Poon CL,Tan JW,Mentiplay BF,Pua YH

    更新日期:2017-01-01 00:00:00

  • Knee osteoarthritis patients with severe nocturnal pain have altered proximal tibial subchondral bone mineral density.

    abstract:OBJECTIVE:Our objective was to investigate relationships between proximal tibial subchondral bone mineral density (BMD) and nocturnal pain in patients with knee osteoarthritis (OA). METHODS:The preoperative knee of 42 patients booked for knee arthroplasty was scanned using quantitative computed tomography (QCT). Pain ...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章

    doi:10.1016/j.joca.2015.04.012

    authors: Burnett WD,Kontulainen SA,McLennan CE,Hazel D,Talmo C,Hunter DJ,Wilson DR,Johnston JD

    更新日期:2015-09-01 00:00:00

  • Prevalence of cam and pincer-type deformities on hip MRI in an asymptomatic young Swiss female population: a cross-sectional study.

    abstract:OBJECTIVES:Femoroacetabular impingement is proposed to cause early osteoarthritis (OA) in the non-dysplastic hip. We previously reported on the prevalence of femoral deformities in a young asymptomatic male population. The aim of this study was to determine the prevalence of both femoral and acetabular types of impinge...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章

    doi:10.1016/j.joca.2013.01.003

    authors: Leunig M,Jüni P,Werlen S,Limacher A,Nüesch E,Pfirrmann CW,Trelle S,Odermatt A,Hofstetter W,Ganz R,Reichenbach S

    更新日期:2013-04-01 00:00:00

  • Standardization of nutrient media for isolated human articular chondrocytes in gelified agarose suspension culture.

    abstract::Human articular cartilage cells were cultured in 1.5% agarose in Dulbecco's modified Eagle's medium (DMEM) with 10% fetal calf serum or in serum-free DMEM with 0.15% bovine serum albumin. 35S-aggrecan synthesis in serum-free DMEM was between 20% and 30% of the value observed in DMEM supplemented with 10% fetal calf se...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章

    doi:10.1016/s1063-4584(05)80016-0

    authors: Verbruggen G,Malfait AM,Dewulf M,Broddelez C,Veys EM

    更新日期:1995-12-01 00:00:00

  • A static, closed and scaffold-free bioreactor system that permits chondrogenesis in vitro.

    abstract:OBJECTIVE:To characterise in vitro engineered cartilaginous constructs made employing a novel static, scaffold-free and closed chamber system. DESIGN:Chondrocytes derived from slaughter age pigs (3-6 months) were seeded at high density (20 x 10(6)) into cylindrical chambers (1.0 x 0.5cm) and were maintained between an...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章

    doi:10.1016/s1063-4584(03)00053-0

    authors: Grogan SP,Rieser F,Winkelmann V,Berardi S,Mainil-Varlet P

    更新日期:2003-06-01 00:00:00

  • The association between reduced knee joint proprioception and medial meniscal abnormalities using MRI in knee osteoarthritis: results from the Amsterdam osteoarthritis cohort.

    abstract:BACKGROUND:Osteoarthritis (OA) of the knee is characterized by pain and activity limitations. In knee OA, proprioceptive accuracy is reduced and might be associated with pain and activity limitations. Although causes of reduced proprioceptive accuracy are divergent, medial meniscal abnormalities, which are highly preva...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章

    doi:10.1016/j.joca.2013.02.002

    authors: van der Esch M,Knoop J,Hunter DJ,Klein JP,van der Leeden M,Knol DL,Reiding D,Voorneman RE,Gerritsen M,Roorda LD,Lems WF,Dekker J

    更新日期:2013-05-01 00:00:00

  • Should subchondral bone turnover be targeted when treating osteoarthritis?

    abstract:OBJECTIVE:Osteoarthritis (OA) is the most common form of arthritic disease, and it is a major cause of disability and impaired quality of life in the elderly. OA is a complex disease of the entire joint, including bone and cartilage, thereby presenting alternative approaches for treatment. This review summarizes emergi...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章,评审

    doi:10.1016/j.joca.2008.01.014

    authors: Karsdal MA,Leeming DJ,Dam EB,Henriksen K,Alexandersen P,Pastoureau P,Altman RD,Christiansen C

    更新日期:2008-06-01 00:00:00

  • Single cell sorting identifies progenitor cell population from full thickness bovine articular cartilage.

    abstract:OBJECTIVE:To date, no approved clinical intervention successfully prevents the progressive degradation of injured articular cartilage that leads to osteoarthritis (OA). Stem/progenitor cell populations within tissues of diarthrodial joint have shown their therapeutic potential in treating OA. However, this potential ha...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章

    doi:10.1016/j.joca.2014.07.002

    authors: Yu Y,Zheng H,Buckwalter JA,Martin JA

    更新日期:2014-09-01 00:00:00

  • Quantitative MRI of parallel changes of articular cartilage and underlying trabecular bone in degeneration.

    abstract:OBJECTIVE:To determine the interrelations between degenerative changes in articular cartilage and underlying trabecular bone during development of osteoarthritis and to test the ability of quantitative magnetic resonance imaging (MRI) to detect those changes. METHODS:Human cadaver patellae were investigated with quant...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章

    doi:10.1016/j.joca.2007.03.019

    authors: Lammentausta E,Kiviranta P,Töyräs J,Hyttinen MM,Kiviranta I,Nieminen MT,Jurvelin JS

    更新日期:2007-10-01 00:00:00

  • Novel biomarkers of intervertebral disc cells and evidence of stem cells in the intervertebral disc.

    abstract:OBJECTIVE:Rat intervertebral disc (IVD) is one of the most commonly used and cost-effective alternative models for human IVD. Many IVD related clinical studies need to be pre-tested on rat IVDs. However, studies on the heterogeneous cell clusters of the rat IVD are inadequate, and a further understanding of the marker ...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章

    doi:10.1016/j.joca.2020.12.005

    authors: Wang J,Huang Y,Huang L,Shi K,Wang J,Zhu C,Li L,Zhang L,Feng G,Liu L,Song Y

    更新日期:2020-12-15 00:00:00

  • Changes in biomechanical properties of tendons and ligaments from joint disuse.

    abstract:OBJECTIVE:The purpose of this paper is to review changes in the biomechanical properties of tendons and ligaments from joint disuse. METHOD:We have reviewed 37 experimental studies on joint disuse, which have been carried out with various models of disuse and with various animals. RESULTS:Immobilization of joints has...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章

    doi:10.1053/joca.1998.0167

    authors: Yasuda K,Hayashi K

    更新日期:1999-01-01 00:00:00

  • Early intervention with Interleukin-1 Receptor Antagonist Protein modulates catabolic microRNA and mRNA expression in cartilage after impact injury.

    abstract:OBJECTIVE:The purpose of this controlled laboratory study was to determine the efficacy of Interleukin-1 Receptor Antagonist Protein (IRAP) treatment as an early intervention strategy by examining the changes in microRNA and mRNA expression in cartilage in an ex-vivo porcine knee joint impact model. METHODS:Custom imp...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章

    doi:10.1016/j.joca.2015.05.010

    authors: Genemaras AA,Reiner T,Huang CY,Kaplan L

    更新日期:2015-11-01 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

  • Serial kinematic analysis of the canine hindlimb joints after deafferentation and anterior cruciate ligament transection.

    abstract:OBJECTIVE AND DESIGN:Transection of the anterior cruciate ligament 2 weeks after ipsilateral hindlimb deafferentation leads to osteoarthritis of the knee joint within 3 weeks. We analyzed the gait of six dogs that underwent this procedure in order to identify kinematic changes that could account for this rapid joint de...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章

    doi:10.1016/s1063-4584(97)80012-x

    authors: Vilensky JA,O'Connor BL,Brandt KD,Dunn EA,Rogers PI

    更新日期:1997-05-01 00:00:00

  • Loss of Vhl in cartilage accelerated the progression of age-associated and surgically induced murine osteoarthritis.

    abstract:OBJECTIVE:To investigate the role of Vhl in maintaining the integrity of articular cartilage and in the development of experimental osteoarthritis (OA). METHOD:Histology of articular cartilage and subchondral bone in both Vhl cKO and WT mice were analyzed by histopathology and micro-CT. Articular cartilage destruction...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章

    doi:10.1016/j.joca.2014.06.031

    authors: Weng T,Xie Y,Yi L,Huang J,Luo F,Du X,Chen L,Liu C,Chen D,Chen L

    更新日期:2014-08-01 00:00:00

  • Ankle motion influences the external knee adduction moment and may predict who will respond to lateral wedge insoles?: an ancillary analysis from the SILK trial.

    abstract:OBJECTIVE:Lateral wedge insoles are a potential simple treatment for medial knee osteoarthritis (OA) patients by reducing the external knee adduction moment (EKAM). However in some patients, an increase in their EKAM is seen. Understanding the role of the ankle joint complex in the response to lateral wedge insoles is ...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章,随机对照试验

    doi:10.1016/j.joca.2015.02.164

    authors: Chapman GJ,Parkes MJ,Forsythe L,Felson DT,Jones RK

    更新日期:2015-08-01 00:00:00

  • Biological actions of curcumin on articular chondrocytes.

    abstract:OBJECTIVES:Curcumin (diferuloylmethane) is the principal biochemical component of the spice turmeric and has been shown to possess potent anti-catabolic, anti-inflammatory and antioxidant, properties. This article aims to provide a summary of the actions of curcumin on articular chondrocytes from the available literatu...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章,评审

    doi:10.1016/j.joca.2009.10.002

    authors: Henrotin Y,Clutterbuck AL,Allaway D,Lodwig EM,Harris P,Mathy-Hartert M,Shakibaei M,Mobasheri A

    更新日期:2010-02-01 00:00:00

  • Effect of glucosamine sulphate on joint space narrowing, pain and function in patients with hip osteoarthritis; subgroup analyses of a randomized controlled trial.

    abstract:OBJECTIVE:Recently we reported that glucosamine sulphate (GS) did not have an effect on the symptoms and progression of primary care patients with hip osteoarthritis (OA). The aim of this present study was to investigate whether there are subgroups of patients with hip OA for whom GS might be an effective therapy. MET...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章,随机对照试验

    doi:10.1016/j.joca.2008.05.022

    authors: Rozendaal RM,Uitterlinden EJ,van Osch GJ,Garling EH,Willemsen SP,Ginai AZ,Verhaar JA,Weinans H,Koes BW,Bierma-Zeinstra SM

    更新日期:2009-04-01 00:00:00

  • Gene expression profiling of chondrocytes from a porcine impact injury model.

    abstract:OBJECTIVE:To identify differentially expressed genes between axially impacted and control articular cartilage taken from porcine patellae maintained in organ culture for 14 days. METHODS:Porcine patellae were impacted perpendicular to the articular surface to create an impact injury. Intact patellae (control and impac...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章

    doi:10.1016/j.joca.2007.12.012

    authors: Ashwell MS,O'Nan AT,Gonda MG,Mente PL

    更新日期:2008-08-01 00:00:00

  • Radiographic progression of knee osteoarthritis is associated with MRI abnormalities in both the patellofemoral and tibiofemoral joint.

    abstract:OBJECTIVE:To investigate patterns of MRI abnormalities in the patellofemoral (PFJ) and tibiofemoral joint (TFJ) and their association with radiographic progression, using hypothesis free analyses. DESIGN:205 patients from the GARP study with symptomatic OA at multiple sites (mean age 60 years, 80% woman, median BMI 26...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章

    doi:10.1016/j.joca.2015.09.021

    authors: de Lange-Brokaar BJ,Bijsterbosch J,Kornaat PR,Yusuf E,Ioan-Facsinay A,Zuurmond AM,Kroon HM,Meulenbelt I,Bloem JL,Kloppenburg M

    更新日期:2016-03-01 00:00:00

  • Cell and matrix morphology in articular cartilage from adult human knee and ankle joints suggests depth-associated adaptations to biomechanical and anatomical roles.

    abstract:OBJECTIVE:Marked differences exist between human knee and ankle joints regarding risks and progression of osteoarthritis (OA). Pathomechanisms of degenerative joint disease may therefore differ in these joints, due to differences in tissue structure and function. Focusing on structural issues, which are design goals fo...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章

    doi:

    authors: Quinn TM,Häuselmann HJ,Shintani N,Hunziker EB

    更新日期:2013-12-01 00:00:00

  • Differential regulation of chondrocyte metabolism by oncostatin M and interleukin-6.

    abstract:OBJECTIVE:To determine the effects of interleukin (IL)-6 and oncostatin M (OSM) added separately or in combination with IL-1beta on human osteoarthritic (OA) chondrocytes in alginate beads. DESIGN:Human chondrocytes were isolated from OA cartilage and cultured in alginate beads for 12 days, in the absence or in the pr...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章

    doi:10.1016/j.joca.2004.06.011

    authors: Sanchez C,Deberg MA,Burton S,Devel P,Reginster JY,Henrotin YE

    更新日期:2004-10-01 00:00:00