Evidence map›Paper›PMID 26522700›Full record

ArticleOsteoarthritis and cartilage2016

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

Z Liu, Y Ren, A J Mirando, C Wang, M J Zuscik, R J O'Keefe, M J Hilton

Open access · greenAbstract read
In one paragraph

Article in Osteoarthritis and cartilage, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
3.0field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Role of Notch signaling pathway in joint homeostasis and osteoarthritis.Frontiers in bioengineering and biotechnology · 2026
    Review
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Research advances in cartilage stem cells markers and induced differentiation.Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology · 2021
    Review
  11. Review
  12. Article
  13. Niches for Skeletal Stem Cells of Mesenchymal Origin.Frontiers in cell and developmental biology · 2020
    Review
  14. Mechanisms of synovial joint and articular cartilage development.Cellular and molecular life sciences : CMLS · 2019
    Review
  15. A Notch in the joint that exacerbates osteoarthritis.Nature reviews. Rheumatology · 2018
    Article
  16. Article
  17. Article
  18. Selection and Investigation of a Primate Model of Spontaneous Degenerative Knee Osteoarthritis, the Cynomolgus Monkey (Macaca Fascicularis).Medical science monitor : international medical journal of experimental and clinical research · 2018
    Article
  19. Review
  20. Building and maintaining joints by exquisite local control of cell fate.Wiley interdisciplinary reviews. Developmental biology · 2017
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 1 country.

Z LiuDepartment of Orthopaedics and Rehabilitation, The Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY 14642, USA; Department of Biology, University of Rochester, Rochester, NY 14642, USA.
Y RenDepartment of Orthopaedic Surgery, Duke Orthopaedic Cellular, Developmental, and Genome Laboratories, Duke University School of Medicine, Durham, NC 27710, USA.
A J MirandoDepartment of Orthopaedics and Rehabilitation, The Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY 14642, USA; Department of Orthopaedic Surgery, Duke Orthopaedic Cellular, Developmental, and Genome Laboratories, Duke University School of Medicine, Durham, NC 27710, USA.
C WangDepartment of Orthopaedics and Rehabilitation, The Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY 14642, USA; Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
M J ZuscikDepartment of Orthopaedics and Rehabilitation, The Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY 14642, USA.
R J O'KeefeDepartment of Orthopaedics and Rehabilitation, The Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY 14642, USA; Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
M J HiltonDepartment of Orthopaedics and Rehabilitation, The Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY 14642, USA; Department of Orthopaedic Surgery, Duke Orthopaedic Cellular, Developmental, and Genome Laboratories, Duke University School of Medicine, Durham, NC 27710, USA; Department of Cell Biology, Duke University School of Medicine, Durham, NC 27710, USA. Electronic address: matthew.hilton@dm.duke.edu.
Duke University · USUniversity of Rochester Medical Center · USWashington University in St. Louis · USUniversity of Rochester · US

Funding

Translating PTH Therapy as an Adjuvant for Structural AllograftingP50AR054041 · NIAMS · UNIVERSITY OF ROCHESTER · PI O'KEEFE, REGIS J · 2006 to 2016
$15.7M
Notch Signaling in Joint Cartilage Maintenance and ArthritisR01AR063071 · NIAMS · UNIVERSITY OF ROCHESTER · PI HILTON, MATTHEW J. · 2012 to 2021
$3.9M
Training in Orthopaedic Researchhttps://apps.era.nih.gov/grantfolder/viewInternalGF.era?applId=8841318&folderId=90T32AR053459 · NIAMS · UNIVERSITY OF ROCHESTER · PI ZUSCIK, MICHAEL J · 2006 to 2017
$3.4M
The University of Rochester Core Center for Musculoskeletal Biology and MedicineP30AR061307 · NIAMS · UNIVERSITY OF ROCHESTER · PI SCHWARZ, EDWARD M. · 2011 to 2015
$3.0M
Notch Signaling in Cartilage DevelopmentR01AR057022 · NIAMS · UNIVERSITY OF ROCHESTER · PI HILTON, MATTHEW J. · 2010 to 2014
$1.7M
Notch Mediated Maintenance and Expansion of Human Mesenchymal Stem CellsR21AR059733 · NIAMS · UNIVERSITY OF ROCHESTER · PI HILTON, MATTHEW J. · 2010 to 2011
$373k
NIAMS NIH HHS AR054041NIAMS NIH HHS AR057022NIAMS NIH HHS AR059733NIAMS NIH HHS AR061307NIAMS NIH HHS AR063071NIAMS NIH HHS P30 AR061307NIAMS NIH HHS P50 AR054041NIAMS NIH HHS R01 AR057022NIAMS NIH HHS R01 AR063071NIAMS NIH HHS R21 AR059733NIAMS NIH HHS T32 AR053459
6 · The paper itself

Abstract

objectiveNotch 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.

methodsTwo 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.

resultsLoss 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.

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

Indexed as

AnimalsArthritis, ExperimentalCartilage, ArticularChondrocytesDisease ProgressionGene Expression Regulation, DevelopmentalMiceMice, TransgenicOsteoarthritisOsteoblastsReceptors, NotchSignal TransductionReceptors, NotchCartilageChondrocytesNotch signalingOsteoarthritisSubchondral boneSynovium

Identifiers

PMID26522700
PMCPMC4799757
OpenAlexW2221959806

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.