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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    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    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

  • Association between KLOTHO gene and hand osteoarthritis in a female Caucasian population.

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    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Zhang F,Zhai G,Kato BS,Hart DJ,Hunter D,Spector TD,Ahmadi KR

    更新日期:2007-06-01 00:00:00

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    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Ikegami D,Iwai T,Ryo S,Gu N,Sugiyama T,Oh I,Yoshikawa H,Tsumaki N

    更新日期:2011-02-01 00:00:00

  • Proteoglycan metabolism and viability of articular cartilage explants as modulated by the frequency of intermittent loading.

    abstract:OBJECTIVE:This study was designed to systematically determine whether and to what extent the frequency of intermittent loading modulates the biosynthesis and release of proteoglycans (PGs), and to assess chondrocyte viability within mature bovine articular cartilage explants exposed to different loading patterns. METH...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Sauerland K,Raiss RX,Steinmeyer J

    更新日期:2003-05-01 00:00:00

  • Forecasting the future burden of opioids for osteoarthritis.

    abstract:OBJECTIVE:To quantify the current national burden of opioids for osteoarthritis (OA) pain in Australia in terms of number of dispensed opioid prescriptions and associated costs, and to forecast the likely burden to the year 2030/31. DESIGN:Epidemiological modelling. METHODS:Published data were obtained on rates of op...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Ackerman IN,Zomer E,Gilmartin-Thomas JF,Liew D

    更新日期:2018-03-01 00:00:00

  • Pain, motor and gait assessment of murine osteoarthritis in a cruciate ligament transection model.

    abstract:OBJECTIVE:The major complaint of Osteoarthritis (OA) patients is pain. However, due to the nature of clinical studies and the limitation of animal studies, few studies have linked function impairment and behavioral changes in OA animal models to cartilage loss and histopathology. Our objective was to study surrogate ma...

    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Ruan MZ,Patel RM,Dawson BC,Jiang MM,Lee BH

    更新日期:2013-09-01 00:00:00

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    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Katz JN,Meredith DS,Lang P,Creel AH,Yoshioka H,Neumann G,Fossel AH,de Pablo P,Losina E

    更新日期:2006-05-01 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

  • Subsets of symptomatic hand osteoarthritis in community-dwelling older adults in the United Kingdom: prevalence, inter-relationships, risk factor profiles and clinical characteristics at baseline and 3-years.

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    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


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

    更新日期:2013-11-01 00:00:00

  • Distinct expression pattern of early- and late-response genes in normal and osteoarthritic human synovial membranes.

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    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Zafarullah M,Martel-Pelletier J,Cloutier JM,Gedamu L,Pelletier JP

    更新日期:1993-07-01 00:00:00

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    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Goebel L,Orth P,Cucchiarini M,Pape D,Madry H

    更新日期:2017-04-01 00:00:00

  • Identification of the pathogenic pathways in osteoarthritic hip cartilage: commonality and discord between hip and knee OA.

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    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Xu Y,Barter MJ,Swan DC,Rankin KS,Rowan AD,Santibanez-Koref M,Loughlin J,Young DA

    更新日期:2012-09-01 00:00:00

  • Preoperative progressive explosive-type resistance training is feasible and effective in patients with hip osteoarthritis scheduled for total hip arthroplasty--a randomized controlled trial.

    abstract:OBJECTIVE:To investigate the efficacy and feasibility of progressive explosive-type resistance training (RT) in patients with osteoarthritis (OA) of the hip scheduled for total hip arthroplasty (THA). METHOD:Randomized controlled trial (1:1) in patients diagnosed with hip OA and scheduled for THA. The intervention gro...

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    pub_type: 杂志文章,随机对照试验


    authors: Hermann A,Holsgaard-Larsen A,Zerahn B,Mejdahl S,Overgaard S

    更新日期:2016-01-01 00:00:00

  • Relationship between arthroscopic joint evaluation and the levels of Coll2-1, Coll2-1NO(2), and myeloperoxidase in the blood and synovial fluid of horses affected with osteochondrosis of the tarsocrural joint.

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    pub_type: 杂志文章


    authors: Verwilghen DR,Enzerink E,Martens A,Franck T,Balligand M,Henrotin Y,Detilleux J,Serteyn D

    更新日期:2011-11-01 00:00:00

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    pub_type: 杂志文章


    authors: Collins JA,Moots RJ,Winstanley R,Clegg PD,Milner PI

    更新日期:2013-11-01 00:00:00

  • WOMAC Osteoarthritis Index--additional dimensions for use in subjects with post-traumatic osteoarthritis of the knee. Western Ontario and MacMaster Universities.

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    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Roos EM,Roos HP,Lohmander LS

    更新日期:1999-03-01 00:00:00

  • Site-dependent changes in structure and function of lapine articular cartilage 4 weeks after anterior cruciate ligament transection.

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    pub_type: 杂志文章


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    更新日期:2014-06-01 00:00:00

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

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    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


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    更新日期:2018-07-01 00:00:00

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    pub_type: 杂志文章


    authors: Iijima H,Aoyama T,Nishitani K,Ito H,Fukutani N,Isho T,Kaneda E,Kuroki H,Matsuda S

    更新日期:2017-08-01 00:00:00

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    pub_type: 杂志文章


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    更新日期:2014-08-01 00:00:00

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    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


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

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    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


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    更新日期:2001-08-01 00:00:00

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    pub_type: 杂志文章


    authors: Xu L,Polur I,Lim C,Servais JM,Dobeck J,Li Y,Olsen BR

    更新日期:2009-07-01 00:00:00

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    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


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    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: James IE,Kumar S,Barnes MR,Gress CJ,Hand AT,Dodds RA,Connor JR,Bradley BR,Campbell DA,Grabill SE,Williams K,Blake SM,Gowen M,Lark MW

    更新日期:2000-11-01 00:00:00

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    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Inoue K,Ushiyama T,Kim Y,Shichikawa K,Nishioka J,Hukuda S

    更新日期:1995-09-01 00:00:00

  • Comparison of 1-year vs 2-year change in regional cartilage thickness in osteoarthritis results from 346 participants from the Osteoarthritis Initiative.

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    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Wirth W,Larroque S,Davies RY,Nevitt M,Gimona A,Baribaud F,Lee JH,Benichou O,Wyman BT,Hudelmaier M,Maschek S,Eckstein F,OA Initiative Investigators Group.

    更新日期:2011-01-01 00:00:00

  • Articular cartilage MR imaging and thickness mapping of a loaded knee joint before and after meniscectomy.

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    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    authors: Song Y,Greve JM,Carter DR,Koo S,Giori NJ

    更新日期:2006-08-01 00:00:00

  • The effects of radial shock waves on gene transfer in rabbit chondrocytes in vitro.

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    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


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    更新日期:2007-11-01 00:00:00

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

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    journal_title:Osteoarthritis and cartilage

    pub_type: 杂志文章


    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