Evidence map›Paper›PMID 38760576›Full record

ArticleNature aging2024

DDX5 inhibits hyaline cartilage fibrosis and degradation in osteoarthritis via alternative splicing and G-quadruplex unwinding.

Qianqian Liu, Mingrui Han, Zhigui Wu, Wenqiang Fu, Jun Ji, Qingqing Liang, Minjia Tan, Linhui Zhai, Jian Gao, Dongquan Shi and 5 more

Abstract read
In one paragraph

Article in Nature aging, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

30 citing papers in PubMed, 1 synthesis or guideline pooled it.

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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

15 authors.

Qianqian Liu *State Key Laboratory of Pharmaceutical Biotechnology and Department of Sports Medicine and Adult Reconstructive Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, School of Life Sciences, Nanjing University, Nanjing, China.
Mingrui Han *State Key Laboratory of Pharmaceutical Biotechnology and Department of Sports Medicine and Adult Reconstructive Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, School of Life Sciences, Nanjing University, Nanjing, China.
Zhigui Wu *Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
Wenqiang Fu *High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, China.
Jun JiNanjing Stomatological Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Qingqing LiangNanjing Stomatological Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Minjia TanState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.ORCID http://orcid.org/0000-0002-6784-9653
Linhui ZhaiState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Jian GaoState Key Laboratory of Pharmaceutical Biotechnology and Department of Sports Medicine and Adult Reconstructive Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, School of Life Sciences, Nanjing University, Nanjing, China.ORCID http://orcid.org/0000-0002-2722-7067
Dongquan ShiDepartment of Sports Medicine and Adult Reconstructive Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.ORCID http://orcid.org/0000-0002-4769-7816
Qing JiangDepartment of Sports Medicine and Adult Reconstructive Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.ORCID http://orcid.org/0000-0002-2552-9686
Ziying SunDepartment of Orthopaedics, Jinling Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
Yuping LaiShanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, China.ORCID http://orcid.org/0000-0001-7445-6738
Qiang XuState Key Laboratory of Pharmaceutical Biotechnology and Department of Sports Medicine and Adult Reconstructive Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, School of Life Sciences, Nanjing University, Nanjing, China. qiangxu@nju.edu.cn.ORCID http://orcid.org/0009-0002-9751-3955
Yang SunState Key Laboratory of Pharmaceutical Biotechnology and Department of Sports Medicine and Adult Reconstructive Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, School of Life Sciences, Nanjing University, Nanjing, China. yangsun@nju.edu.cn.ORCID http://orcid.org/0000-0003-1425-0089

Funding

China Postdoctoral Science Foundation 2023M741642National Natural Science Foundation of China (National Science Foundation of China) 21937005National Natural Science Foundation of China (National Science Foundation of China) 32200995National Natural Science Foundation of China (National Science Foundation of China) 81673436National Natural Science Foundation of China (National Science Foundation of China) 81872877National Natural Science Foundation of China (National Science Foundation of China) 82230116National Natural Science Foundation of China (National Science Foundation of China) 91853109
6 · The paper itself

Abstract

Hyaline cartilage fibrosis is typically considered an end-stage pathology of osteoarthritis (OA), which results in changes to the extracellular matrix. However, the mechanism behind this is largely unclear. Here, we found that the RNA helicase DDX5 was dramatically downregulated during the progression of OA. DDX5 deficiency increased fibrosis phenotype by upregulating COL1 expression and downregulating COL2 expression. In addition, loss of DDX5 aggravated cartilage degradation by inducing the production of cartilage-degrading enzymes. Chondrocyte-specific deletion of Ddx5 led to more severe cartilage lesions in the mouse OA model. Mechanistically, weakened DDX5 resulted in abundance of the Fn1-AS-WT and Plod2-AS-WT transcripts, which promoted expression of fibrosis-related genes (Col1, Acta2) and extracellular matrix degradation genes (Mmp13, Nos2 and so on), respectively. Additionally, loss of DDX5 prevented the unfolding Col2 promoter G-quadruplex, thereby reducing COL2 production. Together, our data suggest that strategies aimed at the upregulation of DDX5 hold significant potential for the treatment of cartilage fibrosis and degradation in OA.

Indexed as

Alternative SplicingDEAD-box RNA HelicasesFibrosisG-QuadruplexesOsteoarthritisAnimalsCartilage, ArticularChondrocytesDisease Models, AnimalHumansMaleMiceDdx5 protein, humanDdx5 protein, mouseDEAD-box RNA Helicases

Identifiers

PMID38760576
PMCPMC11108786

What Socratic 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 Socratic graph.