Evidence map›Paper›PMID 32339698›Full record

ArticleOsteoarthritis and cartilage2020

Suppression of circadian clock protein cryptochrome 2 promotes osteoarthritis.

H Bekki, T Duffy, N Okubo, M Olmer, O Alvarez-Garcia, K Lamia, S Kay, M Lotz

Open access · bronzeAbstract read
In one paragraph

Article in Osteoarthritis and cartilage, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.7field-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

25 citing papers in PubMed, 47 citations in OpenAlex.

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  14. Review
  15. Current Perspective on the Role of the Circadian Clock and Extracellular Matrix in Chronic Lung Diseases.International journal of environmental research and public health · 2023
    Review
  16. Article
  17. Co-regulation of circadian clock genes and microRNAs in bone metabolism.Journal of Zhejiang University. Science. B · 2022
    Review
  18. Genetic Variations within the BovineAnimals : an open access journal from MDPI · 2022
    Article
  19. Article
  20. Rhythm disturbance in osteoarthritis.Cell communication and signaling : CCS · 2022
    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

8 authors at 3 institutions in 1 country.

H BekkiDepartment of Molecular Medicine, Scripps Research, La Jolla, CA, USA.
T DuffyDepartment of Molecular Medicine, Scripps Research, La Jolla, CA, USA.
N OkuboDepartment of Molecular Medicine, Scripps Research, La Jolla, CA, USA.
M OlmerDepartment of Molecular Medicine, Scripps Research, La Jolla, CA, USA.
O Alvarez-GarciaDepartment of Molecular Medicine, Scripps Research, La Jolla, CA, USA.
K LamiaDepartment of Molecular Medicine, Scripps Research, La Jolla, CA, USA.
S KayKeck School of Medicine, University of Southern California, Los Angeles, CA, 90089, USA.
M LotzDepartment of Molecular Medicine, Scripps Research, La Jolla, CA, USA. Electronic address: mlotz@scripps.edu.
Scripps Institution of Oceanography · USScripps Research Institute · USUniversity of Southern California · US

Funding

TISSUE ACQUISITION, MORPHOLOGY, AND CELL CULTUREP01AG007996 · NIA · UNIVERSITY OF CALIFORNIA SAN DIEGO · PI SAH, ROBERT L · 1989 to 2016
$26.0M
Integrative Omics analysis of human cartilage in aging and osteoarthritisR01AG049617 · NIA · SCRIPPS RESEARCH INSTITUTE, THE · PI LOTZ, MARTIN K · 2016 to 2024
$5.6M
NIA NIH HHS P01 AG007996NIA NIH HHS R01 AG049617
6 · The paper itself

Abstract

objectivesAbnormal chondrocyte gene expression promotes osteoarthritis (OA) pathogenesis. A previous RNA-sequencing study revealed that circadian rhythm pathway and expression of core clock gene cryptochrome 2 (CRY2) are dysregulated in human OA cartilage. Here we determined expression patterns and function CRY1 and CRY2.

methodsCRY mRNA and protein expression was analyzed in normal and OA human and mouse cartilage. Mice with deletion of Cry1 or Cry2 were analyzed for severity of experimental OA and to determine genes and pathways that are regulated by Cry.

resultsIn human OA cartilage, CRY2 but not CRY1 staining and mRNA expression was significantly decreased. Cry2 was also suppressed in mice with aging-related OA. Cry2 knock out (KO) but not Cry1 KO mice with experimental OA showed significantly increased severity of histopathological changes in cartilage, subchondral bone and synovium. In OA chondrocytes, the levels of CRY1 and CRY2 and the amplitude of circadian fluctuation were significantly lower. RNA-seq on knee articular cartilage of wild-type and Cry2 KO mice identified 53 differentially expressed genes, including known Cry2 target circadian genes Nr1d1, Nr1d2, Dbp and Tef. Pathway analysis that circadian rhythm and extracellular matrix remodeling were dysregulated in Cry2 KO mice.

conclusionsThese results show an active role of the circadian clock in general, and of CRY2 in particular, in maintaining extracellular matrix (ECM) homeostasis in cartilage. This cell autonomous network of circadian rhythm genes is disrupted in OA chondrocytes. Targeting CRY2 has potential to correct abnormal gene expression patterns and reduce the severity of OA.

Indexed as

AdolescentAdultAgedAnimalsCartilage, ArticularCase-Control StudiesChondrocytesCircadian RhythmCryptochromesExtracellular MatrixFemaleHumansImmunohistochemistryMaleMiceMice, KnockoutCRY1 protein, humanCry1 protein, mouseCRY2 protein, humanCry2 protein, mouseCryptochromesRNA, MessengerChondrocytesCircadian rhythmCryptochrome

Identifiers

PMID32339698
PMCPMC7476803
OpenAlexW2936844253

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.