Evidence map›Paper›PMID 42148297›Full record

ArticleFrontiers in cell and developmental biology2026

Regulation of H-type angiogenesis and permeability in the subchondral bone of osteoarthritis: the role of Slit3 and the Robo4/Rac1-GTP/ROS axis.

Xiaolei Chen, Xiaoxin He, Xue Lin, Jiangbo Yan, Di Xue, Lufei Shao, Gangning Feng, Xin Zhao, Long Ma, Kuanmin Tian and 5 more

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In one paragraph

Article in Frontiers in cell and developmental biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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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

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

15 authors.

Xiaolei Chen *The Third Ward of Orthopaedic Department, General Hospital of Ningxia Medical University, Yinchuan, China.
Xiaoxin He *First Clinical Medical School, Ningxia Medical University, Yinchuan, China.
Xue LinInstitute of Osteoarthropathy, Institute of Medical Sciences, General Hospital of Ningxia Medical University, Yinchuan, China.
Jiangbo YanThe Third Ward of Orthopaedic Department, General Hospital of Ningxia Medical University, Yinchuan, China.
Di XueInstitute of Osteoarthropathy, Institute of Medical Sciences, General Hospital of Ningxia Medical University, Yinchuan, China.
Lufei ShaoThe Neurology Department, General Hospital of Ningxia Medical University, Yinchuan, China.
Gangning FengInstitute of Osteoarthropathy, Institute of Medical Sciences, General Hospital of Ningxia Medical University, Yinchuan, China.
Xin ZhaoThe Third Ward of Orthopaedic Department, General Hospital of Ningxia Medical University, Yinchuan, China.
Long MaThe Third Ward of Orthopaedic Department, General Hospital of Ningxia Medical University, Yinchuan, China.
Kuanmin TianFirst Clinical Medical School, Ningxia Medical University, Yinchuan, China.
Hui WangFirst Clinical Medical School, Ningxia Medical University, Yinchuan, China.
Zhibin LanFirst Clinical Medical School, Ningxia Medical University, Yinchuan, China.
Zhidong LuThe Spinal orthopaedic Department, General Hospital of Ningxia Medical University, Yinchuan, China.
Peng LiThe Third Ward of Orthopaedic Department, General Hospital of Ningxia Medical University, Yinchuan, China.
Qunhua JinThe Third Ward of Orthopaedic Department, General Hospital of Ningxia Medical University, Yinchuan, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Subchondral bone H-type angiogenesis and increased permeability are critical in osteoarthritis (OA) progression, yet the underlying regulatory mechanisms remain unclear. This study utilized proteomic analysis to identify significantly elevated expression of Slit guidance ligand 3 (Slit3) and Ras-related C3 botulinum toxin substrate 1 (Rac1) in the subchondral bone of patients with OA, both associated with angiogenesis and permeability. Experimental validation revealed that Slit3 and Rac1-GTP, rather than total Rac1, drive increased H-type angiogenesis and permeability. To further investigate, we exogenously added Slit3 recombinant protein to mimic the effect of non-ECs secreting Slit3 in the subchondral bone microenvironment on endothelial cells (ECs). Exogenous Slit3 significantly promoted migration, tube formation, and permeability in H-type ECs. An anti-Roundabout guidance receptor 4 (Robo4) antibody inhibited these effects and suppressed Rac1-GTP expression and reactive oxygen species (ROS) levels in ECs. Further investigation revealed that Rac1-GTP and ROS inhibitors could block the effects of exogenous Slit3 on H-type endothelial cell migration, tube formation, and permeability. In in vivo experiments, knockout of Slit3 aggravated early OA in destabilization of the medial meniscus (DMM) mice by altering cartilage and subchondral bone structure but alleviated late-stage OA. Moreover, Slit3 promoted H-type angiogenesis and permeability in the subchondral bone of DMM mice through the Robo4/Rac1-GTP signaling pathway, consistent with

Indexed as

angiogenesisosteoarthritis (OA)Rac1-GTPRobo4Slit3subchondral bonevascular permeability

Identifiers

PMID42148297
PMCPMC13176150

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