Notch signaling in postnatal joint chondrocytes, but not subchondral osteoblasts, is required for articular cartilage and joint maintenance.


OBJECTIVE:Notch signaling has been identified as a critical regulator in cartilage development and joint maintenance, and loss of Notch signaling in all joint tissues results in an early and progressive osteoarthritis (OA)-like pathology. This study investigated the targeted cell population within the knee joint in which Notch signaling is required for normal cartilage and joint integrity. METHODS:Two loss-of-function mouse models were generated with tissue-specific knockout of the core Notch signaling component, RBPjκ. The AcanCre(ERT2) transgene specifically removed Rbpjκ floxed alleles in postnatal joint chondrocytes, while the Col1Cre(2.3kb) transgene deleted Rbpjκ in osteoblast populations, including subchondral osteoblasts. Mutant and control mice were analyzed via histology, immunohistochemistry (IHC), real-time quantitative polymerase chain reaction (qPCR), X-ray, and microCT imaging at multiple time-points. RESULTS:Loss of Notch signaling in postnatal joint chondrocytes results in a progressive OA-like pathology, and triggered the recruitment of non-targeted fibrotic cells into the articular cartilage potentially due to mis-regulated chemokine expression from within the cartilage. Upon recruitment, these fibrotic cells produced degenerative enzymes that may lead to the observed cartilage degradation and contribute to a significant portion of the age-related OA-like pathology. On the contrary, loss of Notch signaling in subchondral osteoblasts did not affect normal cartilage development or joint maintenance. CONCLUSIONS:RBPjκ-dependent Notch signaling in postnatal joint chondrocytes, but not subchondral osteoblasts, is required for articular cartilage and joint maintenance.


Liu Z,Ren Y,Mirando AJ,Wang C,Zuscik MJ,O'Keefe RJ,Hilton MJ




Has Abstract


2016-04-01 00:00:00














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    abstract:OBJECTIVE:The hip and knee joints differ biomechanically in terms of contact stresses, fluid lubrication and wear patterns. These differences may be reflected in the synovial fluid (SF) composition of the two joints, but the nature of these differences remains unknown. The objective was to identify differences in osteo...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Akhbari P,Jaggard MK,Boulangé CL,Vaghela U,Graça G,Bhattacharya R,Lindon JC,Williams HRT,Gupte CM

    更新日期:2019-12-01 00:00:00

  • Cartilage thickness at the posterior medial femoral condyle is increased in femorotibial knee osteoarthritis: a cross-sectional CT arthrography study (Part 2).

    abstract:OBJECTIVE:To evaluate the thickness of cartilage at the posterior aspect of the medial and lateral condyle in Osteoarthritis (OA) knees compared to non-OA knees using computed tomography arthrography (CTA). DESIGN:535 consecutive knee CTAs (mean patient age = 48.7 ± 16.0; 286 males), were retrospectively analyzed. Kne...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Omoumi P,Michoux N,Roemer FW,Thienpont E,Vande Berg BC

    更新日期:2015-02-01 00:00:00

  • Expression of biglycan, decorin and fibromodulin in the hypertrophic phase of experimental osteoarthritis.

    abstract::This study sought to assess the relative levels of the mRNAs of the core proteins of the small proteoglycans (PGs) biglycan, decorin and fibromodulin in the hypertrophic phase of the early osteoarthritis (OA) that follows joint injury. Experimental OA was induced in eight dogs by transection of the anterior cruciate l...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Dourado GS,Adams ME,Matyas JR,Huang D

    更新日期:1996-09-01 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


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

    更新日期:2007-03-01 00:00:00

  • C-reactive protein as a biomarker of emergent osteoarthritis.

    abstract:OBJECTIVE:We evaluated C-reactive protein (C-RP), a quantitative marker of the acute phase response, as a potential biomarker of prevalent and incident osteoarthritis of the knee (OAK). METHODS:Serum C-reactive protein concentrations were characterized with ultrasensitive rate nephelometry in a population-based sample...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Sowers M,Jannausch M,Stein E,Jamadar D,Hochberg M,Lachance L

    更新日期:2002-08-01 00:00:00

  • Prolonged clinical benefit from joint distraction in the treatment of ankle osteoarthritis.

    abstract:OBJECTIVE:Osteoarthritis (OA) is a degenerative disabling joint disease affecting more than 10% of the adult population. No validated disease-modifying treatment is available. Joint distraction is a relatively new approach to the treatment of severe ankle OA. Short-term (3 years) clinical benefit has been proven, but l...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Ploegmakers JJ,van Roermund PM,van Melkebeek J,Lammens J,Bijlsma JW,Lafeber FP,Marijnissen AC

    更新日期:2005-07-01 00:00:00

  • Quantitative imaging of proteoglycan in cartilage using a gadolinium probe and microCT.

    abstract:OBJECTIVE:Micro-computed tomography (microCT) imaging has the potential to allow the three-dimensional (3D) visualization of cartilage morphology. However, cartilage intensity on a microCT image is weak because cartilage does not strongly attenuate X-rays. This work was designed to demonstrate that exposure of cartilag...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Cockman MD,Blanton CA,Chmielewski PA,Dong L,Dufresne TE,Hookfin EB,Karb MJ,Liu S,Wehmeyer KR

    更新日期:2006-03-01 00:00:00

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

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    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


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

    更新日期:2004-10-01 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


    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

  • Mechanism of proteoglycan aggregate degradation in cartilage stimulated with oncostatin M.

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    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Durigova M,Roughley PJ,Mort JS

    更新日期:2008-01-01 00:00:00

  • Avocado soybean unsaponifiables (ASU) suppress TNF-alpha, IL-1beta, COX-2, iNOS gene expression, and prostaglandin E2 and nitric oxide production in articular chondrocytes and monocyte/macrophages.

    abstract:OBJECTIVE:To evaluate the effects of avocado soybean unsaponifiables (ASU) on proinflammatory mediators in chondrocytes and monocyte/macrophage-like cells. DESIGN:To determine the dose response of ASU, chondrocytes (5 x 10(5) cells/well) were incubated at 5% CO(2), 37 degrees C for 72 h with (1) control media alone or...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Au RY,Al-Talib TK,Au AY,Phan PV,Frondoza CG

    更新日期:2007-11-01 00:00:00

  • Marked and rapid change of bone shape in acutely ACL injured knees - an exploratory analysis of the Kanon trial.

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    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章,随机对照试验


    authors: Bowes MA,Lohmander LS,Wolstenholme CBH,Vincent GR,Conaghan PG,Frobell RB

    更新日期:2019-04-01 00:00:00

  • Establishment of a bipotent cell line CL-1 which differentiates into chondrocytes and adipocytes from adult mouse.

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    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Kitamura H

    更新日期:2004-01-01 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


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

    更新日期:2013-04-01 00:00:00

  • Intra-articular hyaluronate in experimental rabbit osteoarthritis can prevent changes in cartilage proteoglycan content.

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    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Hulmes DJ,Marsden ME,Strachan RK,Harvey RE,McInnes N,Gardner DL

    更新日期:2004-03-01 00:00:00

  • Phase-sensitive X-ray imaging of synovial joints.

    abstract:OBJECTIVE:To test the efficacy of phase-sensitive X-ray imaging for intact synovial joints, whereby refraction effects, along with the attenuation of conventional radiography, can be exploited. DESIGN:Intact cadaveric human knee joints were imaged, in the computed tomographic mode, using an analyzer-based X-ray system...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Li J,Zhong Z,Connor D,Mollenhauer J,Muehleman C

    更新日期:2009-09-01 00:00:00

  • Effect of hyaluronic acid (MW 500-730 kDa) on proteoglycan and nitric oxide production in human osteoarthritic chondrocyte cultures exposed to hydrostatic pressure.

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    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Fioravanti A,Cantarini L,Chellini F,Manca D,Paccagnini E,Marcolongo R,Collodel G

    更新日期:2005-08-01 00:00:00

  • The effects of oral glucosamine on joint health: is a change in research approach needed?

    abstract:OBJECTIVE:Oral glucosamine (GlcN) has been widely studied for its potential therapeutic benefits in alleviating the pain and disability of osteoarthritis (OA). Its popularity has grown despite ongoing controversy regarding its effectiveness vs placebo in clinical trials, and lack of information regarding possible mecha...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章,评审


    authors: Block JA,Oegema TR,Sandy JD,Plaas A

    更新日期:2010-01-01 00:00:00

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    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章,meta分析


    authors: Losina E,Dervan EE,Daigle ME,Katz JN

    更新日期:2013-09-01 00:00:00

  • Trabecular bone structure and spatial differences in articular cartilage MR relaxation times in individuals with posterior horn medial meniscal tears.

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    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Kumar D,Schooler J,Zuo J,McCulloch CE,Nardo L,Link TM,Li X,Majumdar S

    更新日期:2013-01-01 00:00:00

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    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Kim HE,Shin Y,Jung IJ,Yang JI,Chun CH,Kim HA,Chun JS

    更新日期:2021-01-21 00:00:00

  • Anterior Cruciate Ligament OsteoArthritis Score (ACLOAS): Longitudinal MRI-based whole joint assessment of anterior cruciate ligament injury.

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    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章,随机对照试验


    authors: Roemer FW,Frobell R,Lohmander LS,Niu J,Guermazi A

    更新日期:2014-05-01 00:00:00

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    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Goldman LH,Tang K,Facchetti L,Heilmeier U,Joseph GB,Nevitt MC,McCulloch CE,Souza RB,Link TM

    更新日期:2016-12-01 00:00:00

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    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    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

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    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Godziuk K,Prado CM,Woodhouse LJ,Forhan M

    更新日期:2019-12-01 00:00:00

  • Effects of treadmill running and limb immobilization on knee cartilage degeneration and locomotor joint kinematics in rats following knee meniscal transection.

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    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Tsai LC,Cooper ES,Hetzendorfer KM,Warren GL,Chang YH,Willett NJ

    更新日期:2019-12-01 00:00:00

  • Body mass index affects knee joint mechanics during gait differently with and without moderate knee osteoarthritis.

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    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Harding GT,Hubley-Kozey CL,Dunbar MJ,Stanish WD,Astephen Wilson JL

    更新日期:2012-11-01 00:00:00

  • Effect of adenovirus-mediated overexpression of bovine ADAMTS-4 and human ADAMTS-5 in primary bovine articular chondrocyte pellet culture system.

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    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Arai M,Anderson D,Kurdi Y,Annis-Freeman B,Shields K,Collins-Racie LA,Corcoran C,DiBlasio-Smith E,Pittman DD,Dorner AJ,Morris E,LaVallie ER

    更新日期:2004-08-01 00:00:00

  • The prevalence of cam hip morphology in a general population sample.

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    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Dickenson EJ,Wall PDH,Hutchinson CE,Griffin DR

    更新日期:2019-03-01 00:00:00

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    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Gale DR,Chaisson CE,Totterman SM,Schwartz RK,Gale ME,Felson D

    更新日期:1999-11-01 00:00:00