Evidence map›Paper›PMID 42704704›Full record

ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2026

Integrative Transcriptomic Profiling Delineates LTBP4-Driven Fibroblast Reprogramming Across the Ossification Continuum of the Ligamentum Flavum.

Xiao Zhang, Tengyao Niu, Yulong Zhao, Zhenguo Liu, Wenbo Gu, Donghui Cao, Yanrong Tian, Haifeng Yuan

Abstract read
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Article in FASEB journal : official publication of the Federation of American Societies for Experimental 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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2 · The registry

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Xiao ZhangGeneral Hospital of Ningxia Medical University, Ningxia, China.
Tengyao NiuNingxia Medical University, Ningxia, China.
Yulong ZhaoNingxia Medical University, Ningxia, China.
Zhenguo LiuNingxia Medical University, Ningxia, China.
Wenbo GuGeneral Hospital of Ningxia Medical University, Ningxia, China.
Donghui CaoNingxia Medical University, Ningxia, China.
Yanrong TianNingxia Medical University, Ningxia, China.
Haifeng YuanGeneral Hospital of Ningxia Medical University, Ningxia, China.

Funding

Natural Science Foundation of Ningxia Province 2023AAC03543
6 · The paper itself

Abstract

To delineate the dynamic transcriptomic landscape of ossification of the ligamentum flavum (OLF) across normal, immature, and mature stages, identify core genes, and screen stage-specific drug candidates. Normal, immature, and mature OLF tissues (nine samples) from three patients with multilevel OLF were collected for RNA-seq. Differential expression, functional enrichment, and dynamic trend analyses were performed. Key genes were validated using an external GEO dataset. Single-cell and spatial transcriptomics were integrated to determine cellular origin and spatial localization. AI-based drug prediction and molecular docking were conducted. Between normal versus immature, 1026 DEGs were identified; between immature versus mature, 713 DEGs; and between normal versus mature, 1285 DEGs. Upregulated genes were enriched in RNA processing and ribosome biogenesis, whereas downregulated genes were enriched in ECM-receptor interaction. LTBP4 showed progressive downregulation during ossification (AUC = 0.88). Single-cell transcriptomics and spatial transcriptomic analysis of a public multi-omics dataset (GSE255942) revealed that LTBP4 is expressed in fibroblasts, with lower expression in ossified than normal tissues. Virtual knockout of Ltbp4 in fibroblasts recapitulated the OLF transcriptomic signature. AI-based drug prediction identified stage-specific candidates; BRD-K59831625 exhibited the lowest binding energy with LTBP4 (-8.9 kcal/mol). Sustained LTBP4 downregulation drives OLF progression, with fibroblasts as core effector cells. Stage-specific drug candidates were identified. These findings provide new targets for molecular diagnosis and precision treatment of OLF.

Indexed as

FibroblastsLatent TGF-beta Binding ProteinsLigamentum FlavumOssification, HeterotopicOsteogenesisTranscriptomeGene Expression ProfilingHumansSpatial TranscriptomicsLatent TGF-beta Binding Proteinsdrug predictionLTBP4ossification of the ligamentum flavumsingle‐cell sequencingspatial transcriptomicsstage‐specific treatmenttranscriptomics

Identifiers

PMID42704704
PMCPMC13549387

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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 OpenQuestion graph.