Evidence map›Paper›PMID 22173325›Full record

ArticleOsteoarthritis and cartilage2012

Depletion of primary cilia in articular chondrocytes results in reduced Gli3 repressor to activator ratio, increased Hedgehog signaling, and symptoms of early osteoarthritis.

C-F Chang, G Ramaswamy, R Serra

Abstract read
In one paragraph

Article in Osteoarthritis and cartilage, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

61 citing papers in PubMed, 98 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Histone Deacetylase 6 (HDAC6) in Ciliopathies: Emerging Insights and Therapeutic Implications.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
  6. Article
  7. Article
  8. Primary cilia are critical for tracheoesophageal septation.Developmental dynamics : an official publication of the American Association of Anatomists · 2024
    Article
  9. [Piezo1 Mediates the Regulation of Substrate Stiffness on Primary Cilia in Chondrocytes].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2024
    Article
  10. Review
  11. Review
  12. Review
  13. Primary Cilia Direct Murine Articular Cartilage Tidemark Patterning Through Hedgehog Signaling and Ambulatory Load.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022
    Article
  14. Ciliary IFT88 Protects Coordinated Adolescent Growth Plate Ossification From Disruptive Physiological Mechanical Forces.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022
    Article
  15. Lef1 ablation alleviates cartilage mineralization following posttraumatic osteoarthritis induction.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  16. Article
  17. Review
  18. Article
  19. Role of Primary Cilia in Skeletal Disorders.Stem cells international · 2022
    Review
  20. Review

1 more citing papers are in PubMed but not listed here.

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

3 authors at 1 institution in 1 country.

C-F ChangDepartment of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35294-0005, USA.
G Ramaswamy
R Serra
University of Alabama at Birmingham · US

Funding

UAB Recessive PKD Research and Translational Core CenterP30DK074038 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI YODER, BRADLEY K. · 2005 to 2019
$16.6M
TGF-Beta in the Pathology and Development of the SpineR01AR053860 · NIAMS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI SERRA, ROSA A. · 2007 to 2017
$3.2M
TGF-beta in the Pathology and Development of the SpineR56AR053860 · NIAMS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI SERRA, ROSA A. · 2020 to 2020
$426k
The Mechanism of TGFBR2 Action in Joint Degeneration.R21AR055110 · NIAMS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI SERRA, ROSA A. · 2008 to 2009
$351k
NIAMS NIH HHS AR053860NIAMS NIH HHS AR055110NIAMS NIH HHS R01 AR053860NIAMS NIH HHS R21 AR055110NIAMS NIH HHS R56 AR053860NIDDK NIH HHS P30 DK074038
6 · The paper itself

Abstract

objectivePrimary cilia are present in almost every cell type including chondrocytes. Studies have shown that defects in primary cilia result in skeletal dysplasia. The purpose of this study was to understand how loss of primary cilia affects articular cartilage.

designIft88 encodes a protein that is required for intraflagellar transport and formation of primary cilia. In this study, we used Col2aCre;Ift88(fl/fl) transgenic mice in which primary cilia were deleted in chondrocytes. Col2aCre;Ift88(fl/fl) articular cartilage was characterized by histological staining, real time RT-PCR, and microindentation. Hedgehog (Hh) signaling was measured by expression of Ptch1 and Gli1 mRNA. The levels of Gli3 proteins were determined by western blot.

resultsCol2aCre;Ift88(fl/fl) articular cartilage was thicker and had increased cell density, likely due to decreased apoptosis during cartilage remodeling. Mutant articular cartilage also showed increased expression of osteoarthritis (OA) markers including Mmp13, Adamts5, ColX, and Runx2. OA was also evident by reduced stiffness in mutant cartilage as measured by microindentation. Up-regulation of Hh signaling, which has been associated with OA, was present in mutant articular cartilage as measured by expression of Ptch1 and Gli1. Col2aCre;Ift88(fl/fl) cartilage also demonstrated reduced Gli3 repressor to activator ratio.

conclusionOur results indicate that primary cilia are required for normal development and maintenance of articular cartilage. It was shown that primary cilia are required for processing full length Gli3 to the truncated repressor form. We propose that OA symptoms in Col2aCre;Ift88(fl/fl) cartilage are due to reduced Hh signal repression by Gli3.

Indexed as

AnimalsArthritis, ExperimentalBiomarkersCartilage, ArticularChondrocytesCiliaHedgehog ProteinsKruppel-Like Transcription FactorsMiceMice, TransgenicNerve Tissue ProteinsOsteoarthritisPatched-1 ReceptorPatched ReceptorsReceptors, Cell SurfaceRNA, MessengerBiomarkersGli1 protein, mouseGli3 protein, mouseHedgehog ProteinsKruppel-Like Transcription FactorsNerve Tissue ProteinsPatched-1 ReceptorPatched ReceptorsPtch1 protein, mouseReceptors, Cell SurfaceRNA, MessengerZinc Finger Protein GLI1Zinc Finger Protein Gli3

Identifiers

PMID22173325
PMCPMC3260404
OpenAlexW2092902622

What OpenQuestion holds

Textmetadata
LicenceTDM
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.