Mechanobiology in Osteoarthritis: From Crosstalk of Mechanosensitive Signaling Pathways to the Intervention Mechanisms and Therapeutic Potential of Exercise.
4 affiliations
- 1School of Clinical Medicine, Southwest Medical University, Luzhou, Sichuan, People's Republic of China.
- 2School of Physical Education, Southwest Medical University, Luzhou, Sichuan, People's Republic of China.
- 3Department of Orthopedics, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, People's Republic of China.
- 4Luzhou Key Laboratory of Orthopedic Disorders, Southwest Medical University, Luzhou, Sichuan, People's Republic of China.
Abstract
Osteoarthritis (OA) is the most prevalent joint degeneration globally. Once considered passive "wear and tear", it is now recognized as a metabolically active, whole-joint disease driven by genetic, metabolic, inflammatory, and mechanical factors. The core pathology is failed mechanotransduction, where a dysregulated mechanosensitive signaling network disrupts joint homeostasis, causing cartilage degradation, synovitis, and pain. This review re-examines OA pathogenesis through network biology, highlighting that OA stems from the dysregulation of a complex mechanosensitive network-including Piezo, Transient Receptor Potential Vanilloid 4 (TRPV4), Integrin-Focal Adhesion Kinase (integrin-FAK), Hippo/yes-associated protein-transcriptional coactivator with PDZ-binding motif (Hippo/YAP-TAZ), and Wingless/Integrated /β-catenin (Wnt/β-catenin) pathways. These pathways engage in extensive crosstalk via shared secondary messengers (calcium ions, reactive oxygen species) to determine cell fate. Furthermore, exercise acts as a physiological "mechanotherapy" to recalibrate this network, shifting cellular responses from catabolic/inflammatory states to anabolic/homeostatic ones. We also explore the translational potential of restoring network balance using precision mechanotherapy, advanced drug delivery, and biomaterials. OA is fundamentally a systemic network failure from failed mechanotransduction. Future therapies should shift from single-target interventions to systemic reprogramming of the dysregulated network. Utilizing biomaterials, smart drug delivery, and personalized exercise can advance OA management from symptomatic relief to active tissue regeneration and disease reversal.
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BibTeX
@article{pu2026mechanobiology,
title = {{Mechanobiology in Osteoarthritis: From Crosstalk of Mechanosensitive Signaling Pathways to the Intervention Mechanisms and Therapeutic Potential of Exercise.}},
author = {Zhenghua Pu and Zhengzhen Yuan and Lei Zhang},
journal = {Journal of inflammation research},
year = {2026},
month = oct,
doi = {10.2147/jir.s651390},
url = {https://europepmc.org/article/MED/42936298},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Mechanobiology in Osteoarthritis: From Crosstalk of Mechanosensitive Signaling Pathways to the Intervention Mechanisms and Therapeutic Potential of Exercise.
AU - Zhenghua Pu
AU - Zhengzhen Yuan
AU - Lei Zhang
PY - 2026
DA - 2026/10/22
JO - Journal of inflammation research
DO - 10.2147/jir.s651390
UR - https://europepmc.org/article/MED/42936298
AB - Osteoarthritis (OA) is the most prevalent joint degeneration globally. Once considered passive "wear and tear", it is now recognized as a metabolically active, whole-joint disease driven by genetic, metabolic, inflammatory, and mechanical factors. The core pathology is failed mechanotransduction, where a dysregulated mechanosensitive signaling network disrupts joint homeostasis, causing cartilage degradation, synovitis, and pain. This review re-examines OA pathogenesis through network biology, highlighting that OA stems from the dysregulation of a complex mechanosensitive network-including Piezo, Transient Receptor Potential Vanilloid 4 (TRPV4), Integrin-Focal Adhesion Kinase (integrin-FAK), Hippo/yes-associated protein-transcriptional coactivator with PDZ-binding motif (Hippo/YAP-TAZ), and Wingless/Integrated /β-catenin (Wnt/β-catenin) pathways. These pathways engage in extensive crosstalk via shared secondary messengers (calcium ions, reactive oxygen species) to determine cell fate. Furthermore, exercise acts as a physiological "mechanotherapy" to recalibrate this network, shifting cellular responses from catabolic/inflammatory states to anabolic/homeostatic ones. We also explore the translational potential of restoring network balance using precision mechanotherapy, advanced drug delivery, and biomaterials. OA is fundamentally a systemic network failure from failed mechanotransduction. Future therapies should shift from single-target interventions to systemic reprogramming of the dysregulated network. Utilizing biomaterials, smart drug delivery, and personalized exercise can advance OA management from symptomatic relief to active tissue regeneration and disease reversal.
SN - 1178-7031
ER -