Evidence map›Paper›PMID 42228211›Full record

ArticleInflammation research : official journal of the European Histamine Research Society ... [et al.]2026

ABCA8 drives bone loss via disrupting Th17/Treg imbalance: a novel immunometabolic target for osteoporosis.

Wenjing Yi, Wenan Xu, Tao Yang, Xiaolin Lyu, Ziting Wang, Leyi Chen, Jingya Zhang, Yiming Zhong, Songlin Wang, Buling Wu

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Article in Inflammation research : official journal of the European Histamine Research Society ... [et al.], 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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0citing papers in PubMed
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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

10 authors.

Wenjing YiShenzhen Clinical College of Stomatology, School of Stomatology, Southern Medical University, Shenzhen, 518000, Guangdong, China.
Wenan XuShenzhen Clinical College of Stomatology, School of Stomatology, Southern Medical University, Shenzhen, 518000, Guangdong, China.
Tao YangShenzhen Clinical College of Stomatology, School of Stomatology, Southern Medical University, Shenzhen, 518000, Guangdong, China.
Xiaolin LyuShenzhen Clinical College of Stomatology, School of Stomatology, Southern Medical University, Shenzhen, 518000, Guangdong, China.
Ziting WangShenzhen Clinical College of Stomatology, School of Stomatology, Southern Medical University, Shenzhen, 518000, Guangdong, China.
Leyi ChenShenzhen Clinical College of Stomatology, School of Stomatology, Southern Medical University, Shenzhen, 518000, Guangdong, China.
Jingya ZhangShenzhen Clinical College of Stomatology, School of Stomatology, Southern Medical University, Shenzhen, 518000, Guangdong, China.
Yiming ZhongShenzhen Clinical College of Stomatology, School of Stomatology, Southern Medical University, Shenzhen, 518000, Guangdong, China.
Songlin WangSalivary Gland Disease Center, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Laboratory of Oral Health, Beijing Stomatological Hospital, Capital Medical University, Beijing, 100070, China. slwang@ccmu.edu.cn.
Buling WuShenzhen Clinical College of Stomatology, School of Stomatology, Southern Medical University, Shenzhen, 518000, Guangdong, China. bulingwu@smu.edu.cn.

Funding

Guangdong Provincial Medical Science and Technology Research Fund Project B2025406
6 · The paper itself

Abstract

backgroundOsteoporosis is a metabolic bone disease characterized by reduced bone mass and microarchitectural deterioration, with complex involvement of molecular networks and immune-associated transcriptional dysregulation.

objectiveThis study aimed to elucidate the immune-associated regulatory features of ATP-binding cassette subfamily A member 8 (ABCA8) in osteoporosis.

methodsDifferential gene expression analysis was performed using the GSE35958 dataset, and 384 up-regulated genes and 1143 down-regulated genes were identified. Weighted gene co-expression network analysis (WGCNA) and machine learning-based feature selection (LASSO, random forest, and Boruta) were applied to identify key osteoporosis-associated genes. Gene set enrichment analysis (GSEA) and single-sample gene set enrichment analysis (ssGSEA) were conducted to explore immune-associated transcriptional signatures, including Th17- and regulatory T cell (Treg)-related signatures. In vivo validation was conducted in ovariectomized (OVX) rats, with gene modulation experiments evaluating bone phenotypes, osteogenic and osteoclastic markers, and inflammatory cytokine profiles.

resultsABCA8 was significantly upregulated in osteoporotic samples and associated with osteoporosis-related transcriptional features. High ABCA8 expression was associated with altered immune-associated signatures, including Th17- and regulatory T cell (Treg)-related transcriptional features, as revealed by ssGSEA. Pathway analyses further linked ABCA8 expression to immune regulation and inflammatory signaling pathways. In OVX rats, ABCA8 knockdown improved trabecular bone microarchitecture, upregulated osteogenic markers (Runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), and osteoprotegerin (OPG)), and downregulated bone resorption markers (receptor activator of nuclear factor κB ligand (RANKL) and tartrate-resistant acid phosphatase (TRAP)). Conversely, ABCA8 overexpression aggravated bone loss and was accompanied by disruption of the Th17/Treg balance and increased levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-17 (IL-17).

conclusionABCA8 is closely associated with osteoporosis-related immune-associated transcriptional alterations and contributes to disease progression through dysregulation of osteoimmune balance. These findings suggest that ABCA8 may represent a potential immunoregulatory target for therapeutic intervention in osteoporosis.

Indexed as

ATP-Binding Cassette TransportersMachine LearningOsteoporosisTh17 CellsT-Lymphocytes, RegulatoryAnimalsBlood CellsDatasets as TopicFemaleFemurGene ExpressionHumansOvariectomyProtein Interaction MapsRatsRats, Sprague-DawleyABCA8 protein, humanATP-Binding Cassette TransportersABCA8Immune-associated signaturesMachine learningOsteoporosisssGSEATh17/Treg balance

Identifiers

PMID42228211
PMCPMC13230258

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.