Evidence mapPaperPMID 41620554Full record

ArticleCell biology and toxicology2026

Synovial macrophage rhoa protects against osteoarthritis by suppressing YAP/IL-17C mediated chondrocyte senescence.

Yizhou Xu, Shuyi Xu, Jiayi Li, Jiaqi Wang, Jie Liang, Jiale Cai, Xianghai Wang, Ying Zou, Gang Deng, Jiasong Guo and 1 more

Abstract read
In one paragraph

Article in Cell biology and toxicology, 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

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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

11 authors.

Yizhou Xu *Department of Spinal Surgery, Orthopedic Medical Center, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.
Shuyi Xu *Department of Histology and Embryology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.
Jiayi Li *Department of Spinal Surgery, Orthopedic Medical Center, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.
Jiaqi Wang *Department of Spinal Surgery, Orthopedic Medical Center, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.
Jie LiangDepartment of Spinal Surgery, Orthopedic Medical Center, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.
Jiale CaiDepartment of Histology and Embryology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.
Xianghai WangDepartment of Histology and Embryology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.
Ying ZouDepartment of Histology and Embryology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.
Gang DengDepartment of Sport Medicine, Ganzhou Hospital-Nanfang Hospital, Southern Medical University, Ganzhou, 341000, China. 461681542@qq.com.ORCID http://orcid.org/0009-0002-9347-0310
Jiasong GuoDepartment of Spinal Surgery, Orthopedic Medical Center, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China. jiasongguo@smu.edu.cn.ORCID http://orcid.org/0000-0002-7885-2903
Lixin ZhuDepartment of Spinal Surgery, Orthopedic Medical Center, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China. zhulixin1966@163.com.ORCID http://orcid.org/0000-0003-3055-3063

Funding

China Postdoctoral Science Foundation 2024M761333Key Research and Development Project of Ganzhou, Jiangxi Province 2023LNS17445
6 · The paper itself

Abstract

objectiveThe GTPase RhoA is known as a regulator involved in cartilage degeneration and subchondral bone remodeling related to osteoarthritis (OA). However, its specific role in synovial macrophages, the key immune cells of OA related tissues, remains entirely unexplored.

methodsHerein, the RhoA expression in human and mouse OA synovium was analyzed. A macrophage-specific RhoA conditional knockout (cKO) mouse model was generated. Histological staining, OARSI scoring, and micro-CT were used to assess cartilage damage, while Western blot, immunofluorescence staining, and ELISA assessed changes in cellular function. Transcriptome sequencing and validation of signaling pathways were conducted using tissues and cells from patients with OA and OA mice.

resultsThe collected results indicate that RhoA expression was significantly upregulated in synovial macrophages from OA patients and mice, correlating with disease severity. Contrary to its reported role in chondrocytes or endothelial cells, macrophage-specific RhoA deletion exacerbated OA, demonstrating enhanced cartilage destruction, subchondral bone loss, and synovitis. RhoA-deficient macrophages exhibited a pro-inflammatory M1 polarization and secreted high levels of IL-17C. This cytokine was necessary and sufficient to induce chondrocyte senescence, as evidenced by increased p53/p21, ROS, mitochondrial dysfunction, and suppressed autophagy, via activation of the PI3K/AKT/mTOR pathway. Mechanistically, RhoA ablation in macrophages activated the Hippo pathway effectors YAP/CCN2, leading to IL-17C transcription, independently of the canonical ROCK pathway.

conclusionIn conclusion, present study reveals a previously unrecognized, protective role for macrophage RhoA in OA. It functions as a critical brake on a novel YAP-IL-17C axis, thereby preserving chondrocyte. This study redefines RhoA's role in joint homeostasis and nominates IL-17C as a potential therapeutic target for OA.

Indexed as

Adaptor Proteins, Signal TransducingCell Cycle ProteinsCellular SenescenceChondrocytesInterleukin-17MacrophagesOsteoarthritisrhoA GTP-Binding Proteinrho GTP-Binding ProteinsSynovial MembraneAnimalsHumansMiceMice, Inbred C57BLMice, KnockoutSignal TransductionAdaptor Proteins, Signal TransducingCell Cycle ProteinsInterleukin-17rhoA GTP-Binding ProteinRhoA protein, mouserho GTP-Binding ProteinsYap1 protein, mouseYAP-Signaling ProteinsChondrocyte SenescenceOsteoarthritisRhoASynovial MacrophageYAP/IL-17C

Identifiers

PMID41620554
PMCPMC12894126

What Socratic 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 Socratic graph.