Evidence map›Paper›PMID 35775626›Full record

ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2022

Mechanical force modulates macrophage proliferation via Piezo1-AKT-Cyclin D1 axis.

Hao Xu, Jiani Guan, Zhichun Jin, Cheng Yin, Shengnan Wu, Wen Sun, Hanwen Zhang, Bin Yan

Open access · bronzeAbstract read
In one paragraph

Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed, 1 pooled it
6.6field-weighted citation impact, top 2% 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

45 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.

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  15. Mechanical stretch promotes sustained proliferation and inflammation in developing human airway smooth muscle.American journal of physiology. Lung cellular and molecular physiology · 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

8 authors at 1 institution in 1 country.

Hao XuDepartment of Orthodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China.
Jiani GuanDepartment of Orthodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China.
Zhichun JinDepartment of Orthodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China.
Cheng YinDepartment of Orthodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China.
Shengnan WuDepartment of Orthodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China.
Wen SunJiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.
Hanwen ZhangSchool of Basic Medical Sciences, Nanjing Medical University, Nanjing, China.
Bin YanDepartment of Orthodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China.ORCID 0000-0001-9169-4615
Nanjing Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Orthodontic tooth movement (OTM) is induced by biomechanical stimuli and facilitated by periodontal tissue remodeling, where multiple immune cells participate in this progression. It has been demonstrated that macrophage is essential for mechanical force-induced tissue remodeling. In this study, we first found that mechanical force significantly induced macrophage proliferation in human periodontal samples and murine OTM models. Yet, how macrophages perceive mechanical stimuli and thereby modulate their biological behaviors remain elusive. To illustrate the mechanisms of mechanical force-induced macrophage proliferation, we subsequently identified Piezo1, a novel mechanosensory ion channel, to modulate macrophage response subjected to mechanical stimuli. Mechanical force upregulates Piezo1 expression in periodontal tissues and cultured bone-marrow-derived macrophages (BMDMs). Remarkably, suppressing Piezo1 with GsMTx4 retarded OTM through reduced macrophage proliferation. Moreover, knockdown of Piezo1 effectively inhibited mechanical force-induced BMDMs proliferation. RNA sequencing was further performed to dissect the underlying mechanisms of Piezo1-mediated mechanotransduction utilizing mechanical stretch system. We revealed that Piezo1-activated AKT/GSK3β signaling was closely associated with macrophage proliferation upon mechanical stimuli. Importantly, Cyclin D1 (Ccnd1) was authenticated as a critical downstream factor of Piezo1 that facilitated proliferation by enhancing Rb phosphorylation. We generated genetically modified mice in which Ccnd1 could be deleted in macrophages in an inducible manner. Conditional ablation of Ccnd1 inhibited periodontal macrophage proliferation and therefore delayed OTM. Overall, our findings highlight that proliferation driven by mechanical force is a key process by which macrophages infiltrate in periodontal tissue during OTM, where Piezo1-AKT-Ccnd1 axis plays a pivotal role.

Indexed as

Cyclin D1Ion ChannelsMacrophagesProto-Oncogene Proteins c-aktAnimalsCell ProliferationHumansMechanotransduction, CellularMiceSignal TransductionCCND1 protein, humanCcnd1 protein, mouseCyclin D1Ion ChannelsPIEZO1 protein, humanPiezo1 protein, mouseProto-Oncogene Proteins c-aktcell proliferationcyclin D1ion channelmacrophagemechanobiologyorthodontics

Identifiers

PMID35775626
PMCPMC12166287
OpenAlexW4283749492

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.