Abstract:
OBJECTIVE:SIRT6, a member of the sirtuin family of nicotinamide adenine dinucleotide (NAD(+))-dependent protein deacetylases, has been implicated as a key factor in aging-related diseases. However, the role of SIRT6 in chondrocytes has not been fully explored. The purpose of this study was to examine the role of SIRT6 in human chondrocytes by inhibiting SIRT6 in vitro. DESIGN:First, the localization of SIRT6 and proliferation cell nuclear antigen (PCNA) in human cartilages was examined by immunohistochemistry. Next, SIRT6 was depleted by RNA interference (RNAi), and the effect of SIRT6 depletion on changes in gene expression, protein levels, proliferation, and senescence in human chondrocytes was assessed. Furthermore, to detect DNA damage and telomere dysfunction, γH2AX foci and telomere dysfunction-induced foci (TIFs) were examined using immunofluorescence microscopy. The protein levels of two mediators for DNA damage induced-senescence, p16 and p21, were examined by western blotting. RESULTS:Immunohistochemical analysis showed SIRT6 was preferentially expressed in the superficial zone chondrocytes and PCNA-positive cluster-forming chondrocytes in the osteoarthritic cartilage tissue samples. Real-time PCR analysis showed that matrix metalloproteinase 1 (MMP-1) and MMP-13 mRNA were significantly increased by SIRT6 inhibition. Moreover, SIRT6 inhibition significantly reduced proliferation and increased senescence associated β-galactosidase (SA-β-Gal)-positive chondrocytes; it also led to increased p16 levels. Immunofluorescence microscopy showed that γH2AX foci and TIFs were increased by SIRT6 inhibition. CONCLUSION:Depletion of SIRT6 in human chondrocytes caused increased DNA damage and telomere dysfunction, and subsequent premature senescence. These findings suggest that SIRT6 plays an important role in the regulation of senescence of human chondrocytes.
journal_name
Osteoarthritis Cartilagejournal_title
Osteoarthritis and cartilageauthors
Nagai K,Matsushita T,Matsuzaki T,Takayama K,Matsumoto T,Kuroda R,Kurosaka Mdoi
10.1016/j.joca.2015.03.024subject
Has Abstractpub_date
2015-08-01 00:00:00pages
1412-20issue
8eissn
1063-4584issn
1522-9653pii
S1063-4584(15)00866-3journal_volume
23pub_type
杂志文章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
更新日期:2014-08-01 00:00:00
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
更新日期:2011-05-01 00:00:00
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
更新日期:2017-07-01 00:00:00
abstract:OBJECTIVE:This study examined the effects of reduced and elevated weight bearing on post-traumatic osteoarthritis (PTOA) development, locomotor joint kinematics, and degree of voluntary activity in rats following medial meniscal transection (MMT). DESIGN:Twenty-one adult rats were subjected to MMT surgery of the left ...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
doi:10.1016/j.joca.2019.08.001
更新日期:2019-12-01 00:00:00
abstract:OBJECTIVE:To investigate individual preferences for physical activity (PA) attributes in adults with chronic knee pain, to identify clusters of individuals with similar preferences, and to identify whether individuals in these clusters differ by their demographic and health characteristics. DESIGN:An adaptive conjoint...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章,多中心研究
doi:10.1016/j.joca.2018.10.002
更新日期:2019-02-01 00:00:00
abstract::In this brief abbreviated review of regulatory issues regarding the development of drugs and or devices for the treatment of osteoarthritis (OA), the steps that are expected by both the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) are discussed. ...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章,评审
doi:10.1016/j.joca.2015.03.010
更新日期:2015-05-01 00:00:00
abstract:OBJECTIVE:To evaluate anterior cruciate ligament transection (ACLT) and destabilization of the medial meniscus (DMM) surgical instability models of osteoarthritis (OA) in the 129/SvEv mouse knee joint. DESIGN:Micro-surgical techniques were used to perform ACLT or DMM under direct visualization. Histological scoring wa...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
doi:10.1016/j.joca.2007.03.006
更新日期:2007-09-01 00:00:00
abstract:OBJECTIVE:The composition and structure of articular cartilage evolves during the development and progression of osteoarthritis (OA) resulting in changing mechanical responses. We aimed to assess the evolution of the intrinsic, large-strain mechanics of human articular cartilage-governed by collagen and proteoglycan an...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
doi:10.1016/j.joca.2018.12.025
更新日期:2019-05-01 00:00:00
abstract:OBJECTIVE:The objective of this work was to compare the measurement properties of three categorical X-ray scoring methods for hip osteoarthritis (OA). METHODS:In data obtained from trials and cohorts, radiographs were evaluated using the Kellgren and Lawrence (KL) grading system, the Osteoarthritis Research Society In...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
doi:10.1016/j.joca.2008.06.009
更新日期:2009-02-01 00:00:00
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 w...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
doi:10.1016/j.joca.2016.09.006
更新日期:2017-06-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to compare the early repair response of cartilage defects in trochlea (TR) and medial femoral condyle (MFC) at 2-3 weeks after bone marrow stimulation. DESIGN:Bilateral full-thickness cartilage defects were generated in central trochlear groove and MFC of skeletally mature rabbits. ...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
doi:10.1016/j.joca.2013.04.010
更新日期:2013-07-01 00:00:00
abstract:OBJECTIVE:This systematic literature review aimed to evaluate the use of conventional radiography (CR) in hand osteoarthritis (OA) and to assess the metric properties of the different radiographic scoring methods. DESIGN:Medical literature databases up to November 2013 were systematically reviewed for studies reportin...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章,评审
doi:10.1016/j.joca.2014.05.026
更新日期:2014-10-01 00:00:00
abstract:OBJECTIVE:This study is to investigate the functions and underlying mechanisms of mesenchymal stem cells (MSCs) underwent stepwise preconditioning in chondrogenic medium before expansion, then further explore their therapeutic effects in a surgically induced osteoarthritis (OA) model. METHODS:MSCs isolated from the ad...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
doi:10.1016/j.joca.2017.05.008
更新日期:2017-09-01 00:00:00
abstract:INTRODUCTION:The Hip disability and Osteoarthritis Outcome Score (HOOS) was constructed in Sweden; this questionnaire has proved to be valid for persons with hip disability with or without hip osteoarthritis (OA) and with high demands of physical function. OBJECTIVE:The objective of this study was to evaluate the inte...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
doi:10.1016/j.joca.2006.06.014
更新日期:2007-01-01 00:00:00
abstract:OBJECTIVES:Determine the depth-varying confined and osmotic compression moduli of normal human articular cartilage from the femoral head, and test whether these moduli are dependent on fixed charge density. METHODS AND RESULTS:Using an automated instrument to allow epifluorescence microscopy analysis during confined c...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
doi:10.1053/joca.2001.0424
更新日期:2001-08-01 00:00:00
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
更新日期:2002-12-01 00:00:00
abstract:OBJECTIVE:To examine the effectiveness of splinting for reducing pain and improving function and health-related quality of life (HR-QoL) in people with thumb carpometacarpal osteoarthritis (CMC OA). DESIGN:The Cochrane Library, MEDLINE, Embase, CINAHL, ISI Web of Science, Scopus and Google Scholar, 3 trial registries ...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章,meta分析
doi:10.1016/j.joca.2018.09.012
更新日期:2019-04-01 00:00:00
abstract:OBJECTIVE:To evaluate the effect of a brace intended to reduce load in patients with medial or lateral compartmental osteoarthritis (OA) and concurrent varus or valgus alignment, respectively. DESIGN:This multi-centre randomized controlled trial (performed 2001-2003) studies the additive effect of a brace intended to ...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1016/j.joca.2006.02.004
更新日期:2006-08-01 00:00:00
abstract:OBJECTIVE:To quantify the precision and accuracy of measurements of joint space width (JSW) and joint space narrowing (JSN) from the medial tibiofemoral compartment of knee radiographs using a simple and easily adaptable protocol. METHODS:Radiographs of a caliper (a surrogate for JSW) were obtained to determine the pr...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
doi:10.1016/s1063-4584(03)00158-4
更新日期:2003-10-01 00:00:00
abstract:OBJECTIVE:To examine the clinical impact of coexisting lateral osteoarthritis (OA) in knees with mild medial OA. DESIGN:In patients with Kellgren/Lawrence (K/L) grade 2 OA in the medial compartment (n = 100; age: 56-89 years; 80.0% female), anteroposterior knee radiography was used to assess the presence of lateral OA...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
doi:10.1016/j.joca.2017.02.801
更新日期:2017-08-01 00:00:00
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
更新日期:2012-07-01 00:00:00
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
更新日期:2013-11-01 00:00:00
abstract:OBJECTIVE:Increased pro-inflammatory cytokines and reactive oxygen and nitrogen species (RONS) occur in osteoarthritis (OA). Oxygen tension can alter the levels of RONS induced by interleukin-1 (IL-1). RONS such as nitric oxide (NO) can alter energy metabolism. The aim of this study was to determine if oxygen tension a...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
doi:10.1016/j.joca.2010.06.004
更新日期:2010-09-01 00:00:00
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
更新日期:2007-03-01 00:00:00
abstract:OBJECTIVE:To evaluate the psychometric properties of the French KOOS physical function (KOOS-PS) and HOOS physical function (HOOS-PS), specifically its feasibility, reliability, construct validity, and responsiveness. METHODS:Consecutive outpatients consulting for primary knee or hip osteoarthritis (OA) in a rheumatol...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
doi:10.1016/j.joca.2009.06.007
更新日期:2009-12-01 00:00:00
abstract:OBJECTIVE:Knee pain relief has been suggested to potentially alter radioanatomic positioning in conventional standing antero-posterior knee radiographs. This study was performed to determine whether this is always the case and in particular if it applied to two recent randomised, placebo-controlled trials showing both ...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
doi:10.1016/j.joca.2006.02.022
更新日期:2006-01-01 00:00:00
abstract:OBJECTIVE:To develop a whole joint scoring system, the Anterior Cruciate Ligament OsteoArthritis Score (ACLOAS), for magnetic resonance imaging (MRI)-based assessment of acute anterior cruciate ligament (ACL) injury and follow-up of structural sequelae, and to assess its reliability. DESIGN:Baseline and follow-up 1.5 ...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.joca.2014.03.006
更新日期:2014-05-01 00:00:00
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
更新日期:2018-07-01 00:00:00
abstract:OBJECTIVE:Osteophytes are non-neoplastic osteo-cartilaginous protrusions growing at the margins of osteoarthritic joints. They can not only be considered as in situ repair tissue, but also represent an excellent in vivo model for induced cartilage repair processes. Our focus was to identify different steps of osteophyt...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
doi:10.1053/joca.2002.0873
更新日期:2003-02-01 00:00:00
abstract:OBJECTIVE:The effect of mechanical injury on chondrocyte viability and matrix degradation was studied. It was proposed that mechanical injury to human cartilage explants results in chondrocyte apoptosis with associated loss of glycosaminoglycans. DESIGN:Full thickness human cartilage explants, 5 mm in diameter were su...
journal_title:Osteoarthritis and cartilage
pub_type: 杂志文章
doi:10.1053/joca.2001.0468
更新日期:2001-11-01 00:00:00