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 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*

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*

Pinch-3 protein is an important constituent of cell membranes, which directly affects the cell morphology and mechanical properties. We observed and compared the change of morphology and cell traction force of glomerular podocytes before and after Pinch-3 gene inhibition by gene interference technology in this experiment. We found that a number of pores appeared on the cell surface, and the cell projected area were increased at the same time, with an approximate average about an increase of 40% after Pinch-3 gene inhibition. The results showed that the cell traction force of glomerular podocytes was significantly reduced, with an approximate average decrease of 40%, the maximum value of the cell traction force was reduced and the distribution of cell traction force became dispersive. All this suggested that after Pinch-3 gene inhibition, some pores created on the cell surface influenced the physical properties of glomerular podocytes and then affected the cell projected area and influenced the formation and distribution of cell traction force of the glomerular podocytes as well.
Adaptor Proteins, Signal Transducing ; genetics ; physiology ; Biomechanical Phenomena ; Cell Movement ; Genetic Engineering ; Humans ; Kidney Glomerulus ; cytology ; LIM Domain Proteins ; genetics ; physiology ; Mechanotransduction, Cellular ; physiology ; Membrane Proteins ; genetics ; physiology ; Podocytes ; cytology ; physiology ; Stress, Mechanical

OBJECTIVETo investigate the effect of cytoskeleton reorganization inhibition with RNA interference on the activation of extracellular signal-regulated kinase (ERK1/2) in primary osteoblasts induced by fluid shear stress (FSS).

METHODSBALB/c mouse primary cultured osteoblasts were isolated by enzyme digestion technique. Osteoblasts were treated with LIM domain kinase 2 (LIM-2) specific siRNA or negative control siRNA, and then were loaded or unloaded by FSS of 1.2 Pa for 0, 5, 15, 30 and 60 min, respectively. The Western blotting was performed to detect the protein expression levels of P-ERK1/2 and ERK1/2, respectively. Two-way ANOVA and one-way ANOVA were used in data analysis.

RESULTSFSS loading for different time (0, 5, 15, 30, 60 min) treated with negative RNA inteference had significant effect on the levels of P-ERK/ERK ratio (0.047 ± 0.031, 0.253 ± 0.137, 0.390 ± 0.155, 0.613 ± 0.123, 0.680 ± 0.108, respectively, P < 0.01). Statistical analysis showed that there was significant interaction between FSS and cytoskeleton reorganization inhibition treated with RNA inteference on the levels of P-ERK/ERK ratio (P < 0.01). The levels of P-ERK/ERK ratio increased when osteoblasts were loaded for 5 - 15 min (0.623 ± 0.129 and 0.623 ± 0.064, respectively, P < 0.05) and returned to baseline at 30 min (0.333 ± 0.086), and then reached the peak at 60 min (0.667 ± 0.064, P < 0.01).

CONCLUSIONSFSS could activate ERK1/2 rapidly in primary cultured osteoblasts. Cytoskeleton reorganization inhibition treated with RNA interference speeded-up the activation of ERK1/2 by FSS, which could increase the sensitivity of ERK1/2 to FSS.

Animals ; Cells, Cultured ; Cytoskeleton ; metabolism ; physiology ; Lim Kinases ; genetics ; metabolism ; Mechanotransduction, Cellular ; Mice ; Mice, Inbred BALB C ; Mitogen-Activated Protein Kinase 1 ; metabolism ; Mitogen-Activated Protein Kinase 3 ; metabolism ; Osteoblasts ; cytology ; enzymology ; Phosphorylation ; RNA Interference ; RNA, Small Interfering ; Stress, Mechanical

Based on single-chip microcomputer, we have established a mechanical strain loading system with multi-channel to study the biological behavior of cultured cells in vitro under mechanical strain. We developed a multi-channel cell strain loading device controlled by single-chip microcomputer. We controlled the vacuum pump with vacuum chamber to make negative pressure changing periodically in the vacuum chamber. The tested cells were seeded on the surface of an elastic membrane mounted on the vacuum chamber, and could be strained or relaxed by cyclic pressure. Since the cells are attached to the surface of the membrane, they presumably experience the same deformation as that was applied to the membrane. The system was easy to carry and to operate, with deformation rate (1%-21%) and frequency (0-0. 5Hz) which could be adjusted correctly according to experimental requirement, and could compare different deformation rate of three channels at the same time. The system ran stably and completely achieved design aims, and provided a method to study the biological behavior of cultured cells attached to the surface of the elastic membrane under mechanical strain in vitro.
Cell Culture Techniques ; instrumentation ; methods ; Computer Simulation ; Equipment Design ; Mechanotransduction, Cellular ; physiology ; Microcomputers ; Stress, Mechanical ; Tensile Strength

Although the basic principles for the function of peripheral auditory system have been known for many years, the molecular mechanisms which affect deafness are not clear. In recent years, the study of hereditary deafness associated mouse models has revealed the molecular basis which is related with the formation and function of the hair bundle and the mechanosensory organelle of hair cell. This review focused on the role of protein network, which is formed by the proteins encoded by the Usher syndrome type 1 genes, in hair-bundle development and mechanotransducer channel gating. And the review also showed how the stereocilia rootlets contribute to the hair bundle's mechanical properties and how the hair bundle produces suppressive masking. Finally, the review revealed multiple roles of the tectorial membrane and extracellular matrix in the hair bundles stimulating in the cochlea.
Animals ; Cochlea ; physiopathology ; Disease Models, Animal ; Extracellular Matrix ; physiology ; Hair Cells, Auditory ; pathology ; Hearing Loss, Sensorineural ; genetics ; Humans ; Mechanotransduction, Cellular ; Mice ; Usher Syndromes ; genetics

We observed how combined mechanical stimuli affect the proliferation and differentiation of pre-osteoblasts. For this research, a bioreactor system was developed that can simultaneously stimulate cells with cyclic strain and ultrasound, each of which is known to effectively stimulate bone tissue regeneration. MC3T3-E1 pre-osteoblasts were chosen for bone tissue engineering due to their osteoblast-like characteristics. 3-D scaffolds were fabricated with polycaprolactone and poly-L-lactic acid using the salt leaching method. The cells were stimulated by the bioreactor with cyclic strain and ultrasound. The bioreactor was set at a frequency of 1.0 Hz and 10% strain for cyclic strain and 1.0 MHz and 30 mW/cm2 for ultrasound. Three experimental groups (ultrasound, cyclic strain, and combined stimulation) and a control group were examined. Each group was stimulated for 20 min/day. Mechanical stimuli did not affect MC3T3-E1 cell proliferation significantly up to 10 days when measured with the cell counting kit-8. However, gene expression analysis of collagen type-I, osteocalcin, RUNX2, and osterix revealed that the combined mechanical stimulation accelerated the matrix maturation of MC3T3-E1 cells. These results indicate that the combined mechanical stimulation can enhance the differentiation of pre-osteoblasts more efficiently than simple stimuli, in spite of no effect on cell proliferation.
Animals ; Bioreactors ; *Bone Regeneration ; Cell Differentiation ; Cell Line ; Cell Proliferation ; Lactic Acid/chemistry ; *Mechanical Processes ; Mechanotransduction, Cellular/physiology ; Mice ; Osteoblasts/cytology/*metabolism ; Polyesters/chemistry ; Polymers/chemistry ; Tissue Engineering/methods ; Tissue Scaffolds/chemistry/utilization