Evidence map›Paper›PMID 34099038›Full record

ArticleStem cell research & therapy2021

Exosomes from miRNA-378-modified adipose-derived stem cells prevent glucocorticoid-induced osteonecrosis of the femoral head by enhancing angiogenesis and osteogenesis via targeting miR-378 negatively regulated suppressor of fused (Sufu).

Kai Nan, Yuankai Zhang, Xin Zhang, Dong Li, Yan Zhao, Zhaopu Jing, Kang Liu, Donglong Shang, Zilong Geng, Lihong Fan

Open access · goldAbstract read
In one paragraph

Article in Stem cell research & therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
9.1field-weighted citation impact, top 1% of its field
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

51 citing papers in PubMed, 71 citations in OpenAlex.

  1. Review
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  3. [Mechanisms of RNA-binding protein phase separation in steroid-associated necrosis of the femoral head].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026
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  10. Roles of skeletal muscle-derived exosomes in osteoporosis.Journal of translational medicine · 2025
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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 at 2 institutions in 1 country.

Kai Nan *Department of Orthopaedics, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157 Xiwu Road, Xi'an, 710004, Shaanxi Province, People's Republic of China.
Yuankai Zhang *Department of Orthopaedics, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157 Xiwu Road, Xi'an, 710004, Shaanxi Province, People's Republic of China.
Xin ZhangDepartment of Orthopaedics, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157 Xiwu Road, Xi'an, 710004, Shaanxi Province, People's Republic of China.
Dong LiDepartment of Orthopaedics, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157 Xiwu Road, Xi'an, 710004, Shaanxi Province, People's Republic of China.
Yan ZhaoDepartment of Orthopaedics, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157 Xiwu Road, Xi'an, 710004, Shaanxi Province, People's Republic of China.
Zhaopu JingDepartment of Orthopaedics, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157 Xiwu Road, Xi'an, 710004, Shaanxi Province, People's Republic of China.
Kang LiuDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, Shaanxi Province, People's Republic of China.
Donglong ShangDepartment of Orthopaedics, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157 Xiwu Road, Xi'an, 710004, Shaanxi Province, People's Republic of China.
Zilong GengDepartment of Orthopaedics, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157 Xiwu Road, Xi'an, 710004, Shaanxi Province, People's Republic of China.
Lihong FanDepartment of Orthopaedics, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157 Xiwu Road, Xi'an, 710004, Shaanxi Province, People's Republic of China. drfan2140@xjtu.edu.cn.ORCID 0000-0002-8864-6732
Second Affiliated Hospital of Xi'an Jiaotong University · CNFirst Affiliated Hospital of Xi'an Jiaotong University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundLocal ischemia and defective osteogenesis are implicated in the progression of glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH). Recent studies have revealed that exosomes released from adipose-derived stem cells (ASCs) play important roles in ONFH therapy. The present study aimed to investigate whether exosomes derived from miR-378-overexpressing ASCs (miR-378-ASCs-Exos) could promote angiogenesis and osteogenesis in GC-induced ONFH.

methodsIn vitro, we investigated the osteogenic potential of miR-378-ASCs-Exos on bone marrow stromal cells (BMSCs) by alkaline phosphatase staining and western blotting. The angiogenic effects of miR-378-ASCs-Exos on human umbilical vein endothelial cells (HUVECs) were examined by evaluating their proliferation, migration, and tube-forming analyses. We identified the underlying mechanisms of miR-378 in osteogenic and angiogenic regulation. In addition, an ONFH rat model was established to explore the effects of miR-378-ASCs-Exos through histological and immunohistochemical staining and micro-CT in vivo.

resultsAdministration of miR-378-ASCs-Exos improved the osteogenic and angiogenic potentials of BMSCs and HUVECs. miR-378 negatively regulated the suppressor of fused (Sufu) and activated Sonic Hedgehog (Shh) signaling pathway, and recombinant Sufu protein reduced the effects triggered by miR-378-ASCs-Exos. In vivo experiments indicated that miR-378-ASCs-Exos markedly accelerated bone regeneration and angiogenesis, which inhibited the progression of ONFH.

conclusionOur study indicated that miR-378-ASCs-Exos enhances osteogenesis and angiogenesis by targeting Sufu to upregulate the Shh signaling pathway, thereby attenuating GC-induced ONFH development.

Indexed as

ExosomesMicroRNAsOsteonecrosisAnimalsFemur HeadGlucocorticoidsHedgehog ProteinsNeovascularization, PhysiologicOsteogenesisRatsRepressor ProteinsStem CellsGlucocorticoidsHedgehog ProteinsMicroRNAsMIRN378 microRNA, ratRepressor ProteinsSuFu protein, ratASCsExosomesmiR-378ONFHShh signalingSufu

Identifiers

PMID34099038
PMCPMC8186190
OpenAlexW3168434032

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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.