OBJECTIVE: To review the role and research progress of mechanotransduction signaling pathway in distraction osteogenesis, so as to provide theoretical basis and reference for clinical treatment. METHODS: The role and research progress of mechanotransduction signaling pathway in distraction osteogenesis were summarized by extensive review of relevant literature at home and abroad. RESULTS: The mechanotransduction signaling pathway plays a central role of "sensation-transformation-execution" in distraction osteogenesis, and activates a series of molecular mechanisms to promote the regeneration and remodeling of bone tissue by integrating external mechanical signals. Mechanical stimuli are converted into mechanotransduction signals through the perception of integrins, Piezo1 ion channels and bone cell networks. Activate downstream molecules are transduce through signal pathways such as Wnt/β-catenin, transforming growth factor β/bone morphogenetic protein-Smad, mitogen-activated protein kinase, protein kinase Hippo-Yes-associated protein/transcriptional coactivator with PDZ-binding motif, and phosphatidylinositol 3-kinase/ protein kinase B, so as to achieve the effects of promoting osteoblasts proliferation, accelerating endochondral ossification, regulating bone resorption and the like, thereby promoting the regeneration of new bone in the distraction area. The study of mechanotransduction signaling pathways in distraction osteogenesis is expected to optimize the mechanical parameters of distraction osteogenesis and provide targeted intervention strategies for accelerating new bone regeneration and mineralization in the distraction zone. However, the specific mechanism of mechanotransduction signaling pathway in distraction osteogenesis remains to be further elucidated, and artificial intelligence and multi-omics analysis may be the future development direction of mechanotransduction signaling pathway. CONCLUSION In distraction osteogenesis, mechanotransduction signal transduction is the core mechanism of bone regeneration in the distraction zone, which regulates cell behavior and tissue regeneration by converting mechanical stimulation into biochemical signals.
Mechanotransduction, Cellular/physiology* ; Osteogenesis, Distraction/methods* ; Humans ; Signal Transduction ; Bone Regeneration ; Animals ; Osteoblasts/metabolism* ; Osteogenesis ; Transforming Growth Factor beta/metabolism* ; Ion Channels/metabolism* ; Integrins/metabolism* ; beta Catenin/metabolism* ; Bone Morphogenetic Proteins/metabolism* ; Smad Proteins/metabolism*

The periodontal ligament (PDL) plays a crucial role in transmitting and dispersing occlusal force, acting as mechanoreceptor for muscle activity during chewing, as well as mediating orthodontic tooth movement. It transforms mechanical stimuli into biological signals, influencing alveolar bone remodeling. Recent research has delved deeper into the biological and mechanical aspects of PDL, emphasizing the importance of understanding its structure and mechanical properties comprehensively. This review focuses on the latest findings concerning both macro- and micro- structural aspects of the PDL, highlighting its mechanical characteristics and factors that influence them. Moreover, it explores the mechanotransduction mechanisms of PDL cells under mechanical forces. Structure-mechanics-mechanotransduction interplay in PDL has been integrated ultimately. By providing an up-to-date overview of our understanding on PDL at various scales, this study lays the foundation for further exploration into PDL-related biomechanics and mechanobiology.
Periodontal Ligament/cytology* ; Humans ; Biomechanical Phenomena ; Mechanotransduction, Cellular/physiology* ; Stress, Mechanical

Piezo2, a mechanosensitive ion channel, serves as a crucial mechanotransducer in dental primary afferent (DPA) neurons and is potentially involved in hypersensitivity to mild mechanical irritations observed in dental patients. Given Piezo2's widespread expression across diverse subpopulations of DPA neurons, this study aimed to characterize the mechanosensory properties of Piezo2-expressing DPA neurons with a focus on distinct features of voltage-gated sodium channels (VGSCs) and neuropeptide profiles. Using whole-cell patch-clamp recordings, we observed mechanically activated action potentials (APs) and classified AP waveforms based on the presence or absence of a hump during the repolarization phase. Single-cell reverse transcription polymerase chain reaction combined with patch-clamp recordings revealed specific associations between AP waveforms and molecular properties, including tetrodotoxin-resistant VGSCs (Na_V1.8 and Na_V1.9) and TRPV1 expression. Reanalysis of the transcriptomic dataset of DPA neurons identified correlations between neuropeptides-including two CGRP isoforms (α-CGRP and β-CGRP), Substance P, and Galanin-and the expression of Na_V1.8 and Na_V1.9, which were linked to defined AP subtypes. These molecular associations were further validated in Piezo2⁺ DPA neurons using fluorescence in situ hybridization. Together, these findings highlight the electrophysiological and neurochemical heterogeneity of Piezo2-expressing DPA neurons and their specialized roles in distinct mechanosensory signal transmission.
Ion Channels/physiology* ; Mechanotransduction, Cellular/physiology* ; Animals ; Neurons, Afferent/metabolism* ; Patch-Clamp Techniques ; Mice ; TRPV Cation Channels/metabolism* ; Action Potentials ; Rats

Mechanical ventilation (MV) is currently widely used in the treatment of respiratory failure and anesthesia surgery, and is a commonly used respiratory support method for critically ill patients; however, improper usage of MV can lead to ventilator-induced lung injury (VILI), which poses a significant threat to patient life. Alveolar epithelial cell (AEC) has the functions of mechanosensation and mechanotransduction. Physiological mechanical stretching is beneficial for maintaining the lineage homeostasis and normal physiological functions of AEC cells, while excessive mechanical stretching can cause damage to AEC cells. Damage to AEC cells is an important aspect in the occurrence and development of VILI. Understanding the effects of mechanical stretching on AEC cells is crucial for developing safe and effective MV strategies, preventing the occurrence of VILI, and improving the clinical prognosis of VILI patients. From the perspective of cell mechanics, this paper aims to briefly elucidate the mechanical properties of AEC cells, mechanosensation and mechanotransduction of mechanical stretching in AEC cells, and the injury and repair of AEC cells under mechanical stretch stimulation, and potential mechanisms with the goal of helping clinical doctors better understand the pathophysiological mechanism of VILI caused by MV, improve their understanding of VILI, provide safer and more effective strategies for the use of clinical MV, and provide theoretical basis for the prevention and treatment of VILI.
Humans ; Mechanotransduction, Cellular ; Ventilator-Induced Lung Injury ; Stress, Mechanical ; Alveolar Epithelial Cells ; Respiration, Artificial/adverse effects* ; Epithelial Cells ; Pulmonary Alveoli/cytology* ; Animals

OBJECTIVE: Psoriasis, a common chronic inflammatory skin condition with genetic underpinnings, is traditionally managed with cupping therapy. Although used historically, the precise mechanical effects and therapeutic mechanisms of cupping in psoriasis remain largely unexamined. This study aimed to evaluate cupping therapy's efficacy for psoriasis and investigate its role in modulating inflammatory responses and cellular metabolism. METHODS: Psoriasis was induced in mice using topical imiquimod (IMQ). The effects of cupping on psoriatic lesions were assessed using the Psoriasis Area and Severity Index score, histology, immunohistochemistry, and immunofluorescence staining. polymerase chain reaction sequencing (RNA-seq) and Western blotting were conducted to examine changes in mRNA expression and the AMP-activated protein kinase (AMPK) signaling pathway. RESULTS: Cupping therapy significantly reduced inflammation, epidermal thickness, and inflammatory cell infiltration in mice with IMQ-induced psoriasis. Immunohistochemistry and immunofluorescence showed lower expression of inflammatory markers and a shift in T-cell populations. RNA-seq and Western blotting indicated that cupping upregulated Piezo1 and activated the AMPK pathway, improving energy metabolism in psoriatic skin. CONCLUSION Cupping therapy reduces epidermal hyperproliferation and inflammation in psoriasis, rebalancing the local immune microenvironment. Mechanistically, cupping promotes calcium influx via Piezo1, activates AMPK signaling, and supports metabolic homeostasis, suggesting therapeutic potential for psoriasis. Please cite this article as: Xi RF, Liu X, Wang Y, Lu HZ, Yuan SJ, Guo DJ, Zhu JY, Li FL, Duan YJ. Mechanosensory activation of Piezo1 via cupping therapy: Harnessing neural networks to modulate AMPK pathway for metabolic restoration in a mouse model of psoriasis. J Integr Med. 2025; 23(6):721-732.
Animals ; Psoriasis/chemically induced* ; Mice ; AMP-Activated Protein Kinases/metabolism* ; Disease Models, Animal ; Cupping Therapy/methods* ; Signal Transduction ; Imiquimod ; Ion Channels/genetics* ; Male ; Mechanotransduction, Cellular

Mechanical signal transduction are crucial for chondrocyte in response to mechanical cues during the growth, development and osteoarthritis (OA) of articular cartilage. Extracellular matrix (ECM) turnover regulates the matrix mechanical microenvironment of chondrocytes. Thus, understanding the mechanotransduction mechanisms during chondrocyte sensing the matrix mechanical microenvironment can develop effective targeted therapy for OA. In recent decades, growing evidences are rapidly advancing our understanding of the mechanical force-dependent cartilage remodeling and injury responses mediated by TRPV4 and PIEZOs. In this review, we highlighted the mechanosensing mechanism mediated by TRPV4 and PIEZOs during chondrocytes sensing mechanical microenvironment of the ECM. Additionally, the latest progress in the regulation of OA by inflammatory signals mediated by TRPV4 and PIEZOs was also introduced. These recent insights provide the potential mechanotheraputic strategies to target these channels and prevent cartilage degeneration associated with OA. This review will shed light on the pathogenesis of articular cartilage, searching clinical targeted therapies, and designing cell-induced biomaterials.
Chondrocytes ; TRPV Cation Channels ; Mechanotransduction, Cellular ; Biocompatible Materials ; Cartilage, Articular

Mechanical stimulus is critical to cardiovascular development during embryogenesis period.The mechanoreceptors of endocardial cells and cardiac myocytes may sense mechanical signals and initiate signal transduction that induce gene expression at a cellular level,and then translate molecular-level events into tissue-level deformations,thus guiding embryo development.This review summarizes the regulatory roles of mechanical signals in the early cardiac development including the formation of heart tube,looping,valve and septal morphogenesis,ventricular development and maturation.Further,we discuss the potential mechanical transduction mechanisms of platelet endothelial cell adhesion molecule 1-vascular endothelial-cadherin-vascular endothelial growth factor receptor 2 complex,primary cilia,ion channels,and other mechanical sensors that affect some cardiac malformations.
Animals ; Heart/embryology* ; Humans ; Mechanotransduction, Cellular ; Myocytes, Cardiac/physiology* ; Vascular Endothelial Growth Factor A/metabolism*

Microenvironmental biophysical factors play a fundamental role in controlling cell behaviors including cell morphology, proliferation, adhesion and differentiation, and even determining the cell fate. Cells are able to actively sense the surrounding mechanical microenvironment and change their cellular morphology to adapt to it. Although cell morphological changes have been considered to be the first and most important step in the interaction between cells and their mechanical microenvironment, their regulatory network is not completely clear. In the current study, we generated silicon-based elastomer polydimethylsiloxane (PDMS) substrates with stiff (15:1, PDMS elastomer vs. curing agent) and soft (45:1) stiffnesses, which showed the Young's moduli of ~450 kPa and 46 kPa, respectively, and elucidated a new path in cytoskeleton re-organization in chondrocytes in response to changed substrate stiffnesses by characterizing the axis shift from the secreted extracellular protein laminin β1, focal adhesion complex protein FAK to microfilament bundling. We first showed the cellular cytoskeleton changes in chondrocytes by characterizing the cell spreading area and cellular synapses. We then found the changes of secreted extracellular linkage protein, laminin β1, and focal adhesion complex protein, FAK, in chondrocytes in response to different substrate stiffnesses. These two proteins were shown to be directly interacted by Co-IP and colocalization. We next showed that impact of FAK on the cytoskeleton organization by showing the changes of microfilament bundles and found the potential intermediate regulators. Taking together, this modulation axis of laminin β1-FAK-microfilament could enlarge our understanding about the interdependence among mechanosensing, mechanotransduction, and cytoskeleton re-organization.
Cell Adhesion ; Chondrocytes ; Cytoskeleton/metabolism* ; Elastomers/metabolism* ; Laminin/metabolism* ; Mechanotransduction, Cellular

The reconstruction of tactile function during the repair of skin damage caused by factors including burns is inseparable from the functional regeneration of tactile receptor Merkel cells. Merkel cells mainly exist in the basal layer of the epidermis and are closely connected with nerves to form Merkel cell-nerve complexes, which play an important role in biological organisms. A large number of studies have shown that Merkel cells conduct precise transmission of mechanical force stimuli through the mechanically gated ion channels PIEZO2, and perform the function of tactile receptors. In this paper, we discussed the characteristics of Merkel cells and analyzed the different subgroups that may possibly exist in this type of cells and their functions, at the same time, we investigated the animal model research of touch-related diseases and the clinical diseases related to touch, revealing the importance of Merkel cell function research.
Animals ; Ion Channels/metabolism* ; Mechanotransduction, Cellular/physiology* ; Merkel Cells/physiology* ; Skin/metabolism* ; Touch/physiology*

Mechanosensitive (MS) channels are extensively studied membrane protein for maintaining intracellular homeostasis through translocating solutes and ions across the membrane, but its mechanisms of channel gating and ion selectivity are largely unknown. Here, we identified the YnaI channel as the Na/K cation-selective MS channel and solved its structure at 3.8 Å by cryo-EM single-particle method. YnaI exhibits low conductance among the family of MS channels in E. coli, and shares a similar overall heptamer structure fold with previously studied MscS channels. By combining structural based mutagenesis, quantum mechanical and electrophysiological characterizations, we revealed that ion selective filter formed by seven hydrophobic methionine (YnaI) in the transmembrane pore determined ion selectivity, and both ion selectivity and gating of YnaI channel were affected by accompanying anions in solution. Further quantum simulation and functional validation support that the distinct binding energies with various anions to YnaI facilitate Na/K pass through, which was defined as binding-block mechanism. Our structural and functional studies provided a new perspective for understanding the mechanism of how MS channels select ions driven by mechanical force.
Cryoelectron Microscopy ; Escherichia coli Proteins ; chemistry ; isolation & purification ; metabolism ; ultrastructure ; Ion Channels ; chemistry ; isolation & purification ; metabolism ; ultrastructure ; Mechanotransduction, Cellular ; Models, Molecular ; Quantum Theory