Evidence map›Paper›PMID 39725007›Full record

ArticleJournal of advanced research2025

Targeting APJ drives BNIP3-PINK1-PARKIN induced mitophagy and improves systemic inflammatory bone loss.

Wentao Wang, Qing Wang, Wenming Li, Hao Xu, Xiaolong Liang, Wei Wang, Ning Li, Huilin Yang, Yaozeng Xu, Jiaxiang Bai and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of advanced research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing 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

10 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Review
  6. Article
  7. Review
  8. Review
  9. Review
  10. Autophagy: regulating the seesaw of bone-fat balance.Frontiers in cell and developmental biology · 2025
    Review
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

12 authors.

Wentao WangDepartment of Orthopaedics, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, Jiangsu, China.
Qing WangDepartment of Orthopaedics, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, Jiangsu, China.
Wenming LiDepartment of Orthopaedics, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, Jiangsu, China.
Hao XuDepartment of Orthopaedics, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, Jiangsu, China.
Xiaolong LiangDepartment of Orthopaedics, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, Jiangsu, China.
Wei WangDepartment of Orthopaedics, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, Jiangsu, China.
Ning LiDepartment of Orthopedics, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230022, China.
Huilin YangDepartment of Orthopaedics, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, Jiangsu, China.
Yaozeng XuDepartment of Orthopaedics, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, Jiangsu, China.
Jiaxiang BaiDepartment of Orthopedics, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230022, China; National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai, China. Electronic address: jxbai1995@ustc.edu.cn.
Shuli YangCollege of Clinical Medicine, Suzhou Vocational Health College, 215009, No.28 Kehua Road, Suzhou city, China. Electronic address: shlyang@szhct.edu.cn.
Dechun GengDepartment of Orthopaedics, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, Jiangsu, China. Electronic address: szgengdc@suda.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionInflammatory diseases, such as diabetes mellitus, rheumatoid arthritis, and inflammatory bowel disease, lead to systemic immune microenvironment disturbances, contributing to bone loss, yet the mechanisms by which specific receptors regulate this process in inflammatory bone loss remain poorly understood. As a G-protein-coupled receptor, the Apelin receptor plays a crucial role in the regulation of inflammation and immune microenvironment. However, the precise mechanisms governing its role in inflammatory bone loss remain incompletely understood.

objectiveThis study aims to investigate how APJ regulates macrophage polarization to mitigate inflammatory bone loss.

methodsLipopolysaccharide induced systemic inflammatory bone loss model in mice was used to explore the relationship between bone loss and osteoclast activation, macrophage polarization and APJ. In vitro studies, Bone marrow derived macrophages and siRNA were used to elucidate the regulatory influence of APJ on the immune microenvironment and osteoclast differentiation, while high-throughput sequencing is leveraged to uncover the underlying mechanisms through which APJ modulates macrophage polarization.

resultsOur study established a link between APJ and macrophage M1 polarization in systemic inflammatory bone loss mice. The activation of APJ effectively mitigated M1 polarization in macrophages, suppressed excessive osteoclast activation, and alleviated systemic inflammatory bone loss. In vitro high-throughput sequencing analysis revealed that APJ modulates macrophage polarization, linking to mitochondrial autophagy and the NOD-like receptor signaling pathway and the involvement of the AMPK and MAPK signaling pathways in signal transduction after APJ activation was also suggested. Subsequent experiments substantiated that APJ predominantly enhances mitophagy and diminishes the accumulation of reactive oxygen species by regulating the AMPK/BNIP3/PINK1/PARKIN axis, thereby suppressing the activation of macrophage M1 polarization and osteoclastogenesis.

conclusionThis study elucidated the underlying mechanism by which APJ modulates macrophage polarization, thereby proposing a new therapeutic target for addressing inflammatory bone loss.

Indexed as

Apelin ReceptorsBone ResorptionInflammationMembrane ProteinsMitophagyProtein KinasesUbiquitin-Protein LigasesAnimalsDisease Models, AnimalLipopolysaccharidesMacrophage ActivationMacrophagesMaleMiceMice, Inbred C57BLOsteoclastsApelin ReceptorsAplnr protein, mouseLipopolysaccharidesMembrane Proteinsparkin proteinProtein KinasesUbiquitin-Protein LigasesAPJBone immune microenvironmentMacrophage polarizationMitophagy

Identifiers

PMID39725007
PMCPMC12793752

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.