Evidence map›Paper›PMID 41080556›Full record

ArticleFrontiers in immunology2025

Piezo1 protects against inflammatory bone loss via a unique Ca

Satoru Shindo, Shin Nakamura, Avery Hawthorne, Alireza Heidari, Maria Rita Pastore, Motoki Okamoto, Maiko Suzuki, Manuel Salinas, Takumi Memida, Dmitriy Minond and 10 more

Abstract read
In one paragraph

Article in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
–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

13 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Article
  4. Review
  5. Review
  6. Review
  7. Article
  8. Yoda molecules agonize PIEZO2.bioRxiv : the preprint server for biology · 2026
    Article
  9. Review
  10. Review
  11. Review
  12. International journal of molecular sciences · 2026
    Article
  13. Review
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

20 authors.

Satoru ShindoDepartment of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University, Fort Lauderdale, FL, United States.
Shin NakamuraDepartment of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University, Fort Lauderdale, FL, United States.
Avery HawthorneDepartment of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University, Fort Lauderdale, FL, United States.
Alireza HeidariDepartment of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University, Fort Lauderdale, FL, United States.
Maria Rita PastoreDepartment of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University, Fort Lauderdale, FL, United States.
Motoki OkamotoDepartment of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University, Fort Lauderdale, FL, United States.
Maiko SuzukiDepartment of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University, Fort Lauderdale, FL, United States.
Manuel SalinasDepartment of Engineering and Technology, College of Engineering and Computing, Nova Southeastern University, Fort Lauderdale, FL, United States.
Takumi MemidaDepartment of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University, Fort Lauderdale, FL, United States.
Dmitriy MinondDepartment of Pharmaceutical Sciences, Barry and Judy Silverman College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL, United States.
Alexander BontempoDepartment of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University, Fort Lauderdale, FL, United States.
Mark CayabyabDepartment of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University, Fort Lauderdale, FL, United States.
Yingzi YangDepartment of Developmental Biology, Harvard School of Dental Medicine, Harvard Stem Cell Institute, Boston, MA, United States.
Janet L CraneDepartment of Orthopedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Maria HernandezDepartment of Periodontology, College of Dental Medicine, Nova Southeastern University, Fort Lauderdale, FL, United States.
Saynur VardarDepartment of Periodontology, College of Dental Medicine, Nova Southeastern University, Fort Lauderdale, FL, United States.
Patrick HardiganCell Therapy Institute, Dr Kiran C. Patel College of Allopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL, United States.
Xiaozhe HanDepartment of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University, Fort Lauderdale, FL, United States.
Steven KaltmanDepartment of Oral and Maxillofacial Surgery, College of Dental Medicine, Nova Southeastern University, Fort Lauderdale, FL, United States.
Toshihisa KawaiDepartment of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University, Fort Lauderdale, FL, United States.

Funding

Gas-Hedgehog signaling in intramembranous bone formation and expansionR01DE025866 · NIDCR · HARVARD MEDICAL SCHOOL · PI Yingzi Yang · 2016 to 2026
$5.3M
Predoctoral Training Grant in PharmacologyT32GM154643 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI Julie A Blendy · 2025 to 2026
$1.1M
Mechanosensing of osteoclasts in periodontitis.F32DE032907 · NIDCR · NOVA SOUTHEASTERN UNIVERSITY · PI SHINDO, SATORU · 2023 to 2024
$174k
NIDCR NIH HHS F32 DE032907NIDCR NIH HHS R01 DE025866NIGMS NIH HHS T32 GM154643
6 · The paper itself

Abstract

Introduction: Bone integrity relies on mechanical stimulation, and its absence, such as in disuse osteoporosis or periodontitis, enhances osteoclast-mediated resorption. Although Piezo1 is a well-characterized mechanosensitive ion channel in several cell types, its function in osteoclast lineage cells has remained unclear. Methods: We examined Piezo1 expression and signaling in pre-osteoclasts (OCs) using mouse models of periodontal bone loss and in vitro differentiation assays. Genetic and pharmacological approaches were applied to manipulate Piezo1 activity. Downstream pathways were assessed with a focus on NFATc1 regulation, Akt phosphorylation, and PP2A activity. The therapeutic potential of the Piezo1 agonist Yoda1 was tested in inflammatory bone loss models. Results: Piezo1 was selectively expressed and functional in pre-OCs, where it acted as a mechanosensor to inhibit RANKL-induced OC-genesis. Activation of Piezo1 suppressed NFATc1 via a Ca Discussion: Our findings redefine Piezo1 as a critical mechanosensor in pre-OCs and establish the Piezo1-PP2A-Akt axis as a novel regulator of NFATc1-driven OC-genesis. These results provide a mechanistic explanation for bone resorption in mechanically compromised states and highlight Piezo1 activation as a therapeutic strategy to mimic mechanical cues and suppress pathological OC-genesis in conditions such as periodontitis, rheumatoid arthritis, and osteoporosis.

Indexed as

Alveolar Bone LossCalciumIon ChannelsOsteoclastsAnimalsBone ResorptionCell DifferentiationDisease Models, AnimalMaleMechanotransduction, CellularMiceMice, Inbred C57BLNFATC Transcription FactorsPeriodontitisProto-Oncogene Proteins c-aktPyrazinesCalciumIon ChannelsNfatc1 protein, mouseNFATC Transcription FactorsPiezo1 protein, mouseProto-Oncogene Proteins c-aktPyrazinesThiadiazolesyoda-1AktmechanosensingosteoclastperiodontitisPiezo1PP2A

Identifiers

PMID41080556
PMCPMC12507952

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.