Evidence map›Paper›PMID 26910618›Full record

ArticleAging cell2016

Acetylation reduces SOX9 nuclear entry and ACAN gene transactivation in human chondrocytes.

Michal Bar Oz, Ashok Kumar, Jinan Elayyan, Eli Reich, Milana Binyamin, Leonid Kandel, Meir Liebergall, Juergen Steinmeyer, Veronique Lefebvre, Mona Dvir-Ginzberg

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Aging cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
4.3field-weighted citation impact, top 6% 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

42 citing papers in PubMed, 73 citations in OpenAlex.

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  16. HU308 Mitigates Osteoarthritis by Stimulating Sox9-Related Networks of Carbohydrate Metabolism.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2023
    Article
  17. Review
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  19. SOX9 in organogenesis: shared and unique transcriptional functions.Cellular and molecular life sciences : CMLS · 2022
    Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 3 countries.

Michal Bar OzLaboratory of Cartilage Biology, Institute of Dental Sciences, Hebrew University of Jerusalem, Jerusalem, Israel.
Ashok KumarLaboratory of Cartilage Biology, Institute of Dental Sciences, Hebrew University of Jerusalem, Jerusalem, Israel.
Jinan ElayyanLaboratory of Cartilage Biology, Institute of Dental Sciences, Hebrew University of Jerusalem, Jerusalem, Israel.
Eli ReichLaboratory of Cartilage Biology, Institute of Dental Sciences, Hebrew University of Jerusalem, Jerusalem, Israel.
Milana BinyaminLaboratory of Cartilage Biology, Institute of Dental Sciences, Hebrew University of Jerusalem, Jerusalem, Israel.
Leonid KandelJoint Replacement and Reconstructive Surgery Unit, Orthopaedic Surgery Complex, Hadassah Mount Scopus Hospital, Jerusalem, Israel.
Meir LiebergallJoint Replacement and Reconstructive Surgery Unit, Orthopaedic Surgery Complex, Hadassah Mount Scopus Hospital, Jerusalem, Israel.
Juergen SteinmeyerLaboratory for Experimental Orthopaedics, Department of Orthopaedic Surgery, University Hospital Giessen & Marburg GmbH, Gießen, Germany.
Veronique LefebvreCleveland Clinic Lerner Research Institute, Cleveland, OH, USA.
Mona Dvir-GinzbergLaboratory of Cartilage Biology, Institute of Dental Sciences, Hebrew University of Jerusalem, Jerusalem, Israel.
Hebrew University of Jerusalem · ILHadassah Academic College · ILCleveland Clinic Lerner College of Medicine · USUniversitätsklinikum Gießen und Marburg · DE

Funding

Transcriptional Control of Sox9R01AR060016 · NIAMS · CLEVELAND CLINIC LERNER COM-CWRU · PI LEFEBVRE, VERONIQUE M · 2010 to 2014
$2.2M
NIAMS NIH HHS R01 AR060016
6 · The paper itself

Abstract

Changes in the content of aggrecan, an essential proteoglycan of articular cartilage, have been implicated in the pathophysiology of osteoarthritis (OA), a prevalent age-related, degenerative joint disease. Here, we examined the effect of SOX9 acetylation on ACAN transactivation in the context of osteoarthritis. Primary chondrocytes freshly isolated from degenerated OA cartilage displayed lower levels of ACAN mRNA and higher levels of acetylated SOX9 compared with cells from intact regions of OA cartilage. Degenerated OA cartilage presented chondrocyte clusters bearing diffused immunostaining for SOX9 compared with intact cartilage regions. Primary human chondrocytes freshly isolated from OA knee joints were cultured in monolayer or in three-dimensional alginate microbeads (3D). SOX9 was hypo-acetylated in 3D cultures and displayed enhanced binding to a -10 kb ACAN enhancer, a result consistent with higher ACAN mRNA levels than in monolayer cultures. It also co-immunoprecipitated with SIRT1, a major deacetylase responsible for SOX9 deacetylation. Finally, immunofluorescence assays revealed increased nuclear localization of SOX9 in primary chondrocytes treated with the NAD SIRT1 cofactor, than in cells treated with a SIRT1 inhibitor. Inhibition of importin β by importazole maintained SOX9 in the cytoplasm, even in the presence of NAD. Based on these data, we conclude that deacetylation promotes SOX9 nuclear translocation and hence its ability to activate ACAN.

Indexed as

AcetylationAgedAggrecansAnimalsCartilage, ArticularCell NucleusCells, CulturedChondrocytesEnhancer Elements, GeneticHEK293 CellsHumansMiceModels, BiologicalProtein BindingProtein StabilityRNA, MessengerACAN protein, humanAggrecansRNA, MessengerSirtuin 1SOX9 Transcription FactoracetylationaggrecanAgingcartilagenucleusosteoarthritisSIRT1SOX9

Identifiers

PMID26910618
PMCPMC4854920
OpenAlexW2278079709

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.