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REVIEW article

Front. Endocrinol.

Sec. Bone Research

Volume 16 - 2025 | doi: 10.3389/fendo.2025.1658967

This article is part of the Research TopicMolecular and Cellular Mechanisms of Bone RemodelingView all 3 articles

The Central Mechanotransducer in Osteoporosis Pathogenesis and Therapy

Provisionally accepted
Chaoyue  LiuChaoyue Liu1jihao  yangjihao yang2zengsheng  dongzengsheng dong3shuqing  zhaoshuqing zhao4Zeng-Hui  TianZeng-Hui Tian1Ying-Ying  LiYing-Ying Li5Yan-Ke  HaoYan-Ke Hao1,5*mingliang  wangmingliang wang3*
  • 1Shandong University of Traditional Chinese Medicine, Jinan, China
  • 2Guizhou University of Traditional Chinese Medicine, Guiyang, China
  • 3Rizhao Hospital of Traditional Chinese Medicine, Rizhao, China
  • 4Shanghai University of Traditional Chinese Medicine, Shanghai, China
  • 5Shandong University of Traditional Chinese Medicine Affiliated Hospital, Jinan, China

The final, formatted version of the article will be published soon.

This review identifies the mechanosensitive ion channel Piezo1 as the central regulator of bone homeostasis. Piezo1 senses mechanical loads in osteocytes, osteoblasts, and bone marrow mesenchymal stem cells (BMSCs), converting them into Ca²⁺-dependent signals that activate key pathways, including CaMKII, YAP/TAZ, Wnt/β-catenin, and ERK. These cascades collectively promote osteoblast differentiation and suppress osteoclastogenesis via OPG/RANKL modulation. Age-related Piezo1 decline impairs bone mechanoresponsiveness, driving both senile and disuse osteoporosis. Piezo1 also integrates bone metabolism with vascular–immune interactions (e.g., promoting VEGFA release from bone marrow macrophages via the CaN/NFAT/HIF-1α pathway) and the gut–bone axis (e.g., intestinal Piezo1 deletion relieves osteoblast proliferation inhibition by reducing serotonin levels). Therapeutically, Piezo1 agonists restore bone mass in osteoporosis models by reactivating mechanotransduction, while physical interventions achieve similar effects. Outstanding challenges include optimizing mechanical parameters (e.g., vibration frequency, ultrasound intensity) for individualized therapy, disentangling pathway crosstalk under aging and inflammation, and developing bone-targeted delivery systems for Piezo1 modulators. Overall, Piezo1 emerges as a pivotal therapeutic target for osteoporosis.

Keywords: Piezo1, Osteoporosis, Mechanotransduction, Bone homeostasis, Therapeutic target

Received: 03 Jul 2025; Accepted: 05 Sep 2025.

Copyright: © 2025 Liu, yang, dong, zhao, Tian, Li, Hao and wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Yan-Ke Hao, Shandong University of Traditional Chinese Medicine, Jinan, China
mingliang wang, Rizhao Hospital of Traditional Chinese Medicine, Rizhao, China

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.