Evidence map›Paper›PMID 42667070›Full record

ArticleBioactive materials2027

A dual-targeting mRNA lipid nanoparticle restores ABCA1-dependent cholesterol homeostasis to promote repair of age-related bone defects.

Mengze Cheng, Kun Xi, Zhengxia Ni, Lingjun Wang, Jincheng Tang, Wei Wang, Ziang Li, Liang Zhou, Xinzhao Jiang, Jie Wu and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Bioactive materials, 2027. 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
–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

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

18 authors.

Mengze ChengDepartment of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, 188 Shizi Road, Suzhou, Jiangsu, China.
Kun XiDepartment of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, 188 Shizi Road, Suzhou, Jiangsu, China.
Zhengxia NiDepartment of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, 188 Shizi Road, Suzhou, Jiangsu, China.
Lingjun WangDepartment of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, 188 Shizi Road, Suzhou, Jiangsu, China.
Jincheng TangDepartment of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, 188 Shizi Road, Suzhou, Jiangsu, China.
Wei WangDepartment of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, 188 Shizi Road, Suzhou, Jiangsu, China.
Ziang LiDepartment of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, 188 Shizi Road, Suzhou, Jiangsu, China.
Liang ZhouDepartment of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, 188 Shizi Road, Suzhou, Jiangsu, China.
Xinzhao JiangDepartment of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, 188 Shizi Road, Suzhou, Jiangsu, China.
Jie WuDepartment of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, 188 Shizi Road, Suzhou, Jiangsu, China.
Qiangqiang GuoDepartment of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, 188 Shizi Road, Suzhou, Jiangsu, China.
Yiwei ZhuDepartment of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, 188 Shizi Road, Suzhou, Jiangsu, China.
Zhengjie TaoDepartment of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, 188 Shizi Road, Suzhou, Jiangsu, China.
Tianyi LiDepartment of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, 188 Shizi Road, Suzhou, Jiangsu, China.
Changdong CuiDepartment of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, 188 Shizi Road, Suzhou, Jiangsu, China.
Wenguo CuiDepartment of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Liang ChenDepartment of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, 188 Shizi Road, Suzhou, Jiangsu, China.
Yong GuDepartment of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Soochow University, 188 Shizi Road, Suzhou, Jiangsu, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cholesterol regulates autophagy and aging, yet its role in bone marrow mesenchymal stem cell (BMSC) senescence remains unclear. We demonstrate that ABCA1 palmitoylation is associated with its lysosomal localization and lysosome-associated cholesterol transport, thereby contributing to autophagy inhibition, senescence, and impaired osteogenesis. However, directly perturbing ABCA1 palmitoylation impaired cholesterol efflux through plasma membrane-localized ABCA1, increased cellular cholesterol accumulation, and inhibited osteogenesis. To selectively depalmitoylate lysosomal ABCA1, we engineered a lysosome-targeted depalmitoylase, RAB7-APT2 (RA), by fusing RAB7 to APT2, the primary depalmitoylase of ABCA1. Aging-cell-targeted low-inflammatory liposomes were synthesized to deliver RA mRNA, yielding dual-targeted lipid nanoparticle (LNP@A). LNP@A selectively modulated lysosomal ABCA1 localization, reduced lysosomal cholesterol accumulation, restored autophagy, and alleviated senescence in aged BMSCs. Consequently, LNP@A enhanced osteogenesis in vitro and improved bone regeneration in an aged rat defect model. These findings reveal a role for ABCA1 spatial regulation in BMSC aging and provide a targeted strategy for age-related bone regeneration.

Indexed as

AutophagyCholesterol metabolismPalmitoylationSenescent bone repair

Identifiers

PMID42667070
PMCPMC13524491

What OpenQuestion holds

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Registered trials

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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.