Evidence map›Paper›PMID 42366405›Full record

ArticleJournal of nanobiotechnology2026

Aptamer-functionalized tetrahedral framework nucleic acid delivery of siBhlhe22 for repairing osteoporotic bone defects via dual modulation of PI3K-Akt signaling and purine metabolism.

Qiaonan Ye, Long Bai, Yue Gao, Shiyi Zeng, Zhiyuan Zhang, Yong Li, Qianke Tao, Maorui Zhang, Yunfeng Lin, Jingang Xiao

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of nanobiotechnology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

Qiaonan Ye *Luzhou Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, The Affiliated Stomatological Hospital, Southwest Medical University, Luzhou, 646000, China.
Long Bai *State Key Laboratory of Oral Diseases, National Center for Stomatology, West China Hospital of Stomatology, National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, 610041, China.
Yue GaoLuzhou Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, The Affiliated Stomatological Hospital, Southwest Medical University, Luzhou, 646000, China.
Shiyi ZengLuzhou Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, The Affiliated Stomatological Hospital, Southwest Medical University, Luzhou, 646000, China.
Zhiyuan ZhangLuzhou Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, The Affiliated Stomatological Hospital, Southwest Medical University, Luzhou, 646000, China.
Yong LiState Key Laboratory of Oral Diseases, National Center for Stomatology, West China Hospital of Stomatology, National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, 610041, China.
Qianke TaoLuzhou Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, The Affiliated Stomatological Hospital, Southwest Medical University, Luzhou, 646000, China.
Maorui ZhangLuzhou Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, The Affiliated Stomatological Hospital, Southwest Medical University, Luzhou, 646000, China. zmr_swmu@sina.com.
Yunfeng LinState Key Laboratory of Oral Diseases, National Center for Stomatology, West China Hospital of Stomatology, National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, 610041, China. yunfenglin@scu.edu.cn.
Jingang XiaoLuzhou Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, The Affiliated Stomatological Hospital, Southwest Medical University, Luzhou, 646000, China. xiaojingang@swmu.edu.cn.

Funding

Luzhou Municipal Science and Technology Program Project 2024JYJ032Luzhou Municipal Science and Technology Program Project 2025MYF002National Natural Science Foundation of China 82370929National Natural Science Foundation of China 82370938Open Project of State Key Laboratory of Oral Diseases SKLOD2025OF05Science and Technology Project of Health Commission of Sichuan Province 24WXXT11Science & Technology Department of Sichuan Province 2024NSFSC2087Youth Innovation Project of Sichuan Medical Association Q2024074
6 · The paper itself

Abstract

Osteoporosis is characterized by an imbalance between bone formation and resorption, and the dysregulated differentiation of bone marrow mesenchymal stem cells (BMSCs) plays a central role. Our previous study identified Bhlhe22 as a key negative regulator of osteogenic differentiation; here, we further validate its role in osteoporotic BMSCs (OP-BMSCs) and investigate its therapeutic potential. Knocking down Bhlhe22 enhanced osteogenesis by upregulating key osteogenic markers (RUNX2, ALP, OPN) and suppressing the PI3K-Akt signaling pathway. To enable targeted delivery of siBhlhe22, we designed an aptamer-functionalized tetrahedral framework nucleic acid-based nanocarrier (Apt19S-tFNA-siBhlhe22, ATS). The ATS system exhibited well-defined nanostructure, excellent biocompatibility, and high cellular uptake efficiency in OP-BMSCs. In vitro, ATS-mediated Bhlhe22 knockdown significantly promoted osteogenic differentiation and matrix mineralization. This effect depended on the inhibition of PI3K-Akt signaling, as demonstrated by rescue experiments using the agonist Recilisib. Non-targeted metabolomics revealed that osteoporosis was associated with disruption of nucleotide and purine metabolism, which was effectively reversed by ATS treatment. Functional studies confirmed that intact purine metabolism, which was essential for ATP production and redox balance, was required for the pro-osteogenic effect of ATS. In an osteoporotic rat bone defect model, ATS delivered via GelMA hydrogel promoted bone regeneration. This was accompanied by in vivo suppression of PI3K-Akt signaling and upregulation of OCN and OPN. Our findings establish a novel gene therapy strategy that targets Bhlhe22 to simultaneously modulate pro-osteogenic signaling and metabolic reprogramming, offering a promising anabolic approach for osteoporosis treatment.

Indexed as

Aptamers, NucleotideOsteoporosisPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktPurinesAnimalsCell DifferentiationMesenchymal Stem CellsOsteogenesisRatsRats, Sprague-DawleySignal TransductionAptamers, NucleotidePhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktpurinePurinesBhlhe22Bone regenerationOsteogenic differentiationOsteoporosisPI3K-Akt signaling pathwayPurine metabolismTetrahedral framework nucleic acids

Identifiers

PMID42366405
PMCPMC13576190

What OpenQuestion holds

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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.