Evidence map›Paper›PMID 39969745›Full record

ArticleScience China. Life sciences2025

Inhibition of KDM6B prevents osteoarthritis by blocking growth plate-like H3K27me3 loss in bivalent genes.

Hao Du, Yao Zhang, Xi Yu, Xuanhe You, Diwei Wu, Ze Du, Yongrui Cai, Zhenyu Luo, Hanpeng Lu, Zhixin Liao and 11 more

Abstract read
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In one paragraph

Article in Science China. Life sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–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

6 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Review
  5. Article
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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

21 authors.

Hao Du *Department of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, 610041, China.
Yao Zhang *Department of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, 610041, China.
Xi YuDepartment of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, 610041, China.
Xuanhe YouDepartment of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, 610041, China.
Diwei WuDepartment of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, 610041, China.
Ze DuDepartment of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, 610041, China.
Yongrui CaiDepartment of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, 610041, China.
Zhenyu LuoDepartment of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, 610041, China.
Hanpeng LuDepartment of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, 610041, China.
Zhixin LiaoDepartment of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, 610041, China.
Bi-Sen DingKey Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University, Chengdu, 610041, China.
Ya ZhaoInstitute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, 225001, China.
Yan WangCollege of Animal Science and Technology, Sichuan Agricultural University, Chengdu, 611130, China.
Ke XiaoDepartment of Lower Limb Surgery of Sichuan Province Orthopedic Hospital, Central Laboratory of Sichuan Province Orthopedic Hospital, Chengdu, 610000, China.
Fan YangBrain Cognition and Brain Disease Institute (BCBDI), Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences (CAS), Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, 518000, China.
Fangji GanSchool of Mechanical Engineering, Sichuan University, Chengdu, 610065, China.
Ning NingDepartment of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, 610041, China.
Jiancheng ZengDepartment of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, 610041, China.
Peiliang ShiGemPharmatech (Chengdu) Co., Ltd., Chengdu, 610000, China.
Zongke ZhouDepartment of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, 610041, China. zongke@126.com.
Shishu HuangDepartment of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, 610041, China. h0794062@scu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Osteoarthritis (OA) is the most prevalent joint disorder occurring with articular cartilage degradation. It includes a switch from an articular to a growth plate chondrocyte phenotype. Here, we investigated the histone modification profiles and found significant H3K27me3 loss in OA, which led to disease-associated gene expression. Surprisingly, these genes were occupied by both H3K27me3 and H3K4me3 in normal chondrocytes, showing a poised bivalent state. Furthermore, we observed the derepression of similar bivalent genes in growth plate chondrocytes. Finally, a KDM6B inhibitor GSK-J4 prevented the H3K27me3 loss and cartilage damage in the rat OA model. Our results reveal an inherited bivalent epigenetic signature on developmental genes that makes articular chondrocytes prone to hypertrophy and contributes to a promising epigenetic therapy for OA.

Indexed as

Growth PlateHistonesJumonji Domain-Containing Histone DemethylasesOsteoarthritisAnimalsAzepinesBenzazepinesCartilage, ArticularChondrocytesDisease Models, AnimalEpigenesis, GeneticHumansMalePyrimidinesRatsRats, Sprague-DawleyAzepinesBenzazepinesGSK-J4HistonesJumonji Domain-Containing Histone DemethylasesKDM6B protein, humanPyrimidinesbivalencygrowth plateH3K27me3histone modificationsosteoarthritis

Identifiers

PMID39969745

What OpenQuestion holds

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Registered trials

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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.