Evidence map›Paper›PMID 41684294›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026

Single-Cell Atlas of Subchondral Bone Marrow Lesions Reveals Proteostasis Dysfunction as a Druggable Mechanism for Early Osteoarthritis.

Hailun Xu, Ting He, Yu Qian, Jia Li, Bowei Ni, Xiaojie Xu, Huanbo Wang, Peng Wang, Guoqing Cao, Siqi Ying and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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.

Hailun XuInstitute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, P. R. China.
Ting HeInstitute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, P. R. China.
Yu QianSuzhou Laboratory of Precision Health and Data Science, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P. R. China.
Jia LiDivision of Orthopaedic Surgery, Department of Orthopedics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P. R. China.
Bowei NiInstitute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, P. R. China.
Xiaojie XuInstitute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, P. R. China.
Huanbo WangInstitute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, P. R. China.
Peng WangInstitute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, P. R. China.
Guoqing CaoInstitute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, P. R. China.
Siqi YingInstitute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, P. R. China.
Guangyu DingInstitute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, P. R. China.
Rong WangDivision of Orthopaedic Surgery, Department of Orthopedics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P. R. China.
Zenghui GuSuzhou Laboratory of Precision Health and Data Science, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P. R. China.
Wei LiShandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, P. R. China.
Zhentao ManShandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, P. R. China.
Houfeng ZhengSuzhou Laboratory of Precision Health and Data Science, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P. R. China.
Zhaohua ZhuClinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, P. R. China.
Zhen LiAO Research Institute Davos, Davos Platz, Switzerland.
Qingjun MengFaculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
Chao ZhengInstitute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, P. R. China.
Liu YangInstitute of Orthopedic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, P. R. China.ORCID https://orcid.org/0000-0002-6498-4702

Funding

National Natural Science Foundation of China 82130070Shaanxi Province Health Science and Technology Innovation Capability Enhancement Program 2025TD-14
6 · The paper itself

Abstract

Subchondral bone marrow lesions (BMLs) constitute a pathognomonic imaging feature of both incipient and progressive osteoarthritis (OA). However, the pathological features and molecular mechanisms underlying BMLs remain poorly characterized. Here, we innovatively established and dynamically characterized a standardized mouse model, simulating human BMLs on magnetic resonance imaging (MRI) that correlates significantly with cartilage degeneration, while revealing substantial aberrant bone matrix accumulation within BML regions. By establishing an osteochondral single-cell atlas of mouse knee joints during BML development, we found that proteasome dysfunction and abnormal secretion of misfolded collagen, driven by dysregulated heat shock protein 70 (HSP70) and deubiquitinase 19 (USP19) expression in osteoarthritic subchondral osteoblasts, constitute a key mechanism of BML formation. Furthermore, cell-cell communication and Col10a1-Cre; R26

Indexed as

Bone MarrowOsteoarthritisProteostasisAnimalsChondrocytesDisease Models, AnimalHumansMagnetic Resonance ImagingMaleMiceOsteoblastsSingle-Cell Analysisbone marrow lesionschondrocyte hypertrophymisfolded collagenosteoarthritissingle‐cell RNA sequencing

Identifiers

PMID41684294
PMCPMC13159136

What OpenQuestion holds

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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.