Piezo1 protects against inflammatory bone loss via a unique Ca2+-independent mechanism in osteoclasts
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.
Authors
- Janet L. Crane (ORCID: https://orcid.org/0000-0001-7713-0936)
- Maria Rita Pastore
- Dmitriy Minond (ORCID: https://orcid.org/0000-0003-2473-5944)
- Shin Nakamura (ORCID: https://orcid.org/0000-0001-7427-8636)
- Alexander Bontempo (ORCID: https://orcid.org/0000-0001-7628-9590)
- Takumi Memida (ORCID: https://orcid.org/0009-0004-9524-9462)
- Motoki Okamoto (ORCID: https://orcid.org/0000-0002-3759-5031)
- Alireza Heidari (ORCID: https://orcid.org/0000-0002-5266-1041)
- A. B. Hawthorne (ORCID: https://orcid.org/0009-0005-3490-0001)
- Toshihisa Kawai (ORCID: https://orcid.org/0000-0003-3310-3818)
- Patrick C. Hardigan (ORCID: https://orcid.org/0000-0001-6965-1766)
- Satoru Shindo (ORCID: https://orcid.org/0000-0003-0478-9363)
- Maria Hernandez (ORCID: https://orcid.org/0000-0003-4931-4388)
- Saynur Vardar (ORCID: https://orcid.org/0009-0002-8804-4843)
- Mark J. Cayabyab (ORCID: https://orcid.org/0000-0002-7803-8098)
- Xiaozhe Han (ORCID: https://orcid.org/0000-0001-8357-1471)
- M. Suzuki (ORCID: https://orcid.org/0000-0002-1732-0663)
- Steven Kaltman
- Manuel Salinas
- Yingzi Yang
Institutions
- University of Wyoming (US)
- Wyoming State Department of Health (US)
- Johns Hopkins University (US)
- Nova Southeastern University (US)
- Johns Hopkins Medicine (US)
- Harvard Stem Cell Institute (US)
Publication Details
- Journal
- Frontiers in Immunology
- Published
- 2025-09-25
- DOI
- https://doi.org/10.3389/fimmu.2025.1661538
- Citations
- 5
- Primary Topic
- Erythrocyte Function and Pathophysiology
- Type
- article
- Field-Weighted Citation Impact
- 5.82