Evidence map›Paper›PMID 36915132›Full record

ArticleJournal of nanobiotechnology2023

Mechanical force induces macrophage-derived exosomal UCHL3 promoting bone marrow mesenchymal stem cell osteogenesis by targeting SMAD1.

Panjun Pu, Shengnan Wu, Kejia Zhang, Hao Xu, Jiani Guan, Zhichun Jin, Wen Sun, Hanwen Zhang, Bin Yan

Open access · goldFull text read
In one paragraph

Article in Journal of nanobiotechnology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
6.8field-weighted citation impact, top 3% 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

33 citing papers in PubMed, 44 citations in OpenAlex.

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  20. Risk factors for the development of heterotopic ossification of the elbow in children with untreated chronic Monteggia fractures: a radiographic review of 274 cases.Journal of orthopaedics and traumatology : official journal of the Italian Society of Orthopaedics and Traumatology · 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

9 authors at 1 institution in 1 country.

Panjun Pu *Department of Orthodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, 210000, China.
Shengnan Wu *Department of Orthodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, 210000, China.
Kejia ZhangDepartment of Orthodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, 210000, China.
Hao XuDepartment of Orthodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, 210000, China.
Jiani GuanDepartment of Orthodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, 210000, China.
Zhichun JinDepartment of Orthodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, 210000, China.
Wen SunJiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, 210000, China.
Hanwen ZhangSchool of Basic Medical Sciences, Nanjing Medical University, Nanjing, 210000, China. hanwenzhang@njmu.edu.cn.
Bin YanDepartment of Orthodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, 210000, China. byan@njmu.edu.cn.
Nanjing Medical University · CN

Funding

Basic Research Program of Jiangsu Province BK20211250Key Medical Research Projects of Jiangsu Health Commission ZDA2020003Key Research and Development Program of Jiangsu Province BE2022795National Natural Science Foundation of China 82071143National Natural Science Foundation of China 82270361Natural Science Research Project of Universities in Jiangsu Province 22KJA310002Priority Academic Program Development of Jiangsu Higher Education Institutions PAPD, 2018-87
6 · The paper itself

Abstract

backgroundOrthodontic tooth movement (OTM), a process of alveolar bone remodelling, is induced by mechanical force and regulated by local inflammation. Bone marrow-derived mesenchymal stem cells (BMSCs) play a fundamental role in osteogenesis during OTM. Macrophages are mechanosensitive cells that can regulate local inflammatory microenvironment and promote BMSCs osteogenesis by secreting diverse mediators. However, whether and how mechanical force regulates osteogenesis during OTM via macrophage-derived exosomes remains elusive.

resultsMechanical stimulation (MS) promoted bone marrow-derived macrophage (BMDM)-mediated BMSCs osteogenesis. Importantly, when exosomes from mechanically stimulated BMDMs (MS-BMDM-EXOs) were blocked, the pro-osteogenic effect was suppressed. Additionally, compared with exosomes derived from BMDMs (BMDM-EXOs), MS-BMDM-EXOs exhibited a stronger ability to enhance BMSCs osteogenesis. At in vivo, mechanical force-induced alveolar bone formation was impaired during OTM when exosomes were blocked, and MS-BMDM-EXOs were more effective in promoting alveolar bone formation than BMDM-EXOs. Further proteomic analysis revealed that ubiquitin carboxyl-terminal hydrolase isozyme L3 (UCHL3) was enriched in MS-BMDM-EXOs compared with BMDM-EXOs. We went on to show that BMSCs osteogenesis and mechanical force-induced bone formation were impaired when UCHL3 was inhibited. Furthermore, mothers against decapentaplegic homologue 1 (SMAD1) was identified as the target protein of UCHL3. At the mechanistic level, we showed that SMAD1 interacted with UCHL3 in BMSCs and was downregulated when UCHL3 was suppressed. Consistently, overexpression of SMAD1 rescued the adverse effect of inhibiting UCHL3 on BMSCs osteogenesis.

conclusionsThis study suggests that mechanical force-induced macrophage-derived exosomal UCHL3 promotes BMSCs osteogenesis by targeting SMAD1, thereby promoting alveolar bone formation during OTM.

Indexed as

Mesenchymal Stem CellsMicroRNAsSmad1 ProteinUbiquitin ThiolesteraseCell DifferentiationMacrophagesOsteogenesisProteomicsMicroRNAsSmad1 ProteinUbiquitin ThiolesteraseExosomesMacrophagesMechanical forceOrthodontic tooth movementOsteogenesisSMAD1UCHL3

Identifiers

PMID36915132
PMCPMC10012474
OpenAlexW4324128850

What OpenQuestion holds

Textfull text, public
LicenceCC BY
measurements read71
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 OpenQuestion graph.