Objective To summarize the role of Piezo mechanosensitive ion channels in the osteoarticular system, in order to provide reference for subsequent research. Methods Extensive literature review was conducted to summarize the structural characteristics, gating mechanisms, activators and blockers of Piezo ion channels, as well as their roles in the osteoarticular systems. Results The osteoarticular system is the main load-bearing and motor tissue of the body, and its ability to perceive and respond to mechanical stimuli is one of the guarantees for maintaining normal physiological functions of bones and joints. The occurrence and development of many osteoarticular diseases are closely related to abnormal mechanical loads. At present, research shows that Piezo mechanosensitive ion channels differentiate towards osteogenesis by responding to stretching stimuli and regulating cellular Ca2+ influx signals; and it affects the proliferation and migration of osteoblasts, maintaining bone homeostasis through cellular communication between osteoblasts-osteoclasts. Meanwhile, Piezo1 protein can indirectly participate in regulating the formation and activity of osteoclasts through its host cells, thereby regulating the process of bone remodeling. During mechanical stimulation, the Piezo1 ion channel maintains bone homeostasis by regulating the expressions of Akt and Wnt1 signaling pathways. The sensitivity of Piezo1/2 ion channels to high strain mechanical signals, as well as the increased sensitivity of Piezo1 ion channels to mechanical transduction mediated by Ca2+ influx and inflammatory signals in chondrocytes, is expected to become a new entry point for targeted prevention and treatment of osteoarthritis. But the specific way mechanical stimuli regulate the physiological/pathological processes of bones and joints still needs to be clarified. Conclusion Piezo mechanosensitive ion channels give the osteoarticular system with important abilities to perceive and respond to mechanical stress, playing a crucial mechanical sensing role in its cellular fate, bone development, and maintenance of bone and cartilage homeostasis.
ObjectiveTo discuss the effect of Piezo1 mechanically sensitive protein in migration process of mouse MC3T3-E1 osteoblast cells.MethodsThe 5th-10th generation mouse MC3T3-E1 osteoblasts were divided into Piezo1-small interfering RNA (siRNA) transfection group (group A), negative control group (group B), and blank control group (group C). Piezo1-siRNA or negative control siRNA was transfected into mouse MC3T3-E1 osteoblasts by siRNA transfection reagent, respectively; group C was only added with siRNA transfection reagent; and the cell morphology was observed under inverted phase contrast microscope and fluorescence microscope, and the transfection efficiency was calculated. The expression of Piezo1 protein was detected by immunofluorescence staining and Western blot. Transwell cell migration assay and cell scratch assay were used to detect the migration of MC3T3-E1 osteoblasts after Piezo1-siRNA transfection.ResultsAfter 48 hours of transfection, group A showed a slight increase in cell volume and mutant growth, but cell colonies decreased, suspension cells increased and cell fragments increased when compared with untransfected cells. Under fluorescence microscope, green fluorescence was observed in MC3T3-E1 osteoblasts of group B, and the transfection efficiency was 68.56%±4.12%. Immunofluorescence staining and Western blot results showed that the expression level of Piezo1 protein in group A was significantly lower than that in groups B and C (P<0.05); there was no significant difference between group B and group C (P>0.05). Transwell cell migration assay and cell scratch assay showed that the number of cells per hole and the scratch healing rate of cells cultured for 1-4 days in group A were significantly lower than those in groups B and C (P<0.05); there was no significant difference between group B and group C (P>0.05).ConclusionPiezo1 knocked down by siRNA can inhibit the migration ability of MC3T3-E1 osteoblast cells.
Objective To review the role of the mechanosensitive ion channel Piezo1 in osteoarthritis (OA) pathogenesis and summarize recent advances in its clinical transformation as a potential therapeutic target. Methods The recent domestic and international research literature was reviewed. Recent studies on Piezo1 in chondrocyte injury, inflammation, extracellular matrix degradation, and osteophyte formation were analyzed, along with Piezo1-targeted inhibitors, activators, and modulators. Results Piezo1 senses abnormal mechanical stress and mediates Ca2+ influx, activating PI3K/AKT/mTOR and MAPK/ERK signaling pathways, thereby promoting chondrocyte apoptosis, impaired autophagy, and matrix degradation. Preclinical studies suggest that GsMTx4, Piezo1-siRNA, Dooku1, and artemisinin may confer chondroprotective effects, but their specificity, stability, delivery efficiency, and safety require further verification. Conclusion Piezo1 is a critical link between mechanical stress and OA progression, representing a potential therapeutic target. Future research should focus on elucidating mechanisms, developing highly specific modulators and targeted delivery systems, and conducting rigorous preclinical and clinical studies to promote clinical transformation.
Objective To investigate the mechanism of the mechanosensitive ion channel Piezo1 in microglial ferroptosis following spinal cord injury (SCI), and to assess the effects of Piezo1 inhibition on ameliorating the injury microenvironment and promoting neurological functional recovery. Methods Primary microglia cells were extracted from neonatal 1-2 days C57BL/6 mice and divided into control group, Yoda1 (Piezo1 agonist) group, and Yoda1+GsMTx4 (Piezo1 inhibitor) group. Live/dead cell staining, reactive oxygen species (ROS) fluorescence staining, 5, 5’, 6, 6’-tetrachloro-1, 1’, 3, 3’-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) mitochondrial membrane potential detection, and transmission electron microscopy were utilized to assess microglial ferroptosis and mitochondrial functional characteristics. SPF female C57BL/6 mice aged 6 to 8 weeks were used to detect the expression of Piezo1 at different time points after SCI by Western blot, and the two time points with no significant change and the most significant change in Piezo1 expression after SCI were selected for subsequent experiments. T8, T9 SCI models were established by modified Allen’s method, and were divided into sham operation group, injury group, and injury+shPiezo1 group (Piezo1-targeted interfering virus AAV-shPiezo1 was injected in situ to knock down the expression of Piezo1 14 days before modeling). Colocalization of Piezo1 with microglial markers purinergic receptor P2Y12 (P2ry12), and the expressions of glutathione peroxidase 4 (GPX4) and acyl coenzyme A synthetase long chain member 4 (ACSL4) were observed by immunofluorescence staining. Basso Mouse Scale (BMS) score was used to assess hindlimb motor function in mice. The level of ROS was detected by dihydroethidium (DHE) staining; the content of malondialdehyde (MDA) was detected by MDA kit; the levels of tumor necrosis factor α (TNF-α) and interleukin 10 (IL-10) were detected by ELISA assay; the pathological morphology of spinal cord was observed by HE staining. Results In vitro experiments showed that compared with the control group, the Yoda1 group had typical ultrastructural changes of ferroptosis, such as increased microglial cell death, enhanced ROS fluorescence, mitochondrial membrane potential depolarization, mitochondrial shrinkage and mitochondrial cristae breakage (all P<0.05), while the GsMTx4 group could partially reverse the above effects (P<0.05). In vivo experiments demonstrated that the expression of Piezo1 in spinal cord tissue was up-regulated sequentially after SCI, and reached the peak on the 7th day after SCI (P<0.05), and it was mainly localized in P2ry12-positive microglia. Compared with the injury group, in the injury+shPiezo1 group, the expression of ferroptosis core protein GPX4 in microglia was increased, the expression of ACSL4 was decreased, the levels of ROS and MDA in spinal cord tissue were decreased (P<0.05), the level of pro-inflammatory factor TNF-α was decreased, and the level of anti-inflammatory factor IL-10 was increased (P<0.05). In addition, the BMS score was significantly higher than that of the injury group (P<0.05) from the 14th day after operation, and the spinal cord tissue structure was relatively well preserved, and the cavity area was reduced. Conclusion SCI activates the Piezo1 channel in microglia, triggering mitochondrial dysfunction and mediating cellular ferroptosis, thereby aggravating secondary neuroinflammation. Targeted inhibition of Piezo1 effectively blocks the ferroptosis process, ameliorates the immune microenvironment, and promotes tissue repair and locomotor functional recovery after SCI.
Self-powered wearable piezoelectric sensing devices demand flexibility and high voltage electrical properties to meet personalized health and safety management needs. Aiming at the characteristics of piezoceramics with high piezoelectricity and low flexibility, this study designs a high-performance piezoelectric sensor based on multi-phase barium titanate (BTO) flexible piezoceramic film, namely multi-phase BTO sensor. The substrate-less self-supported multi-phase BTO films had excellent flexibility and could be bent 180° at a thickness of 33 μm, and exhibited good bending fatigue resistance in 1 × 104 bending cycles at a thickness of 5 μm. The prepared multi-phase BTO sensor could maintain good piezoelectric stability after 1.2 × 104 piezoelectric cycle tests. Based on the flexibility, high piezoelectricity, wearability, portability and battery-free self-powered characteristics of this sensor, the developed smart mask could monitor the respiratory signals of different frequencies and amplitudes in real time. In addition, by mounting the sensor on the hand or shoulder, different gestures and arm movements could also be detected. In summary, the multi-phase BTO sensor developed in this paper is expected to develop convenient and efficient wearable sensing devices for physiological health and behavioral activity monitoring applications.
Radiopharmaceutical dynamic imaging typically necessitates intravenous injection via the bolus method. However, manual bolus injection carries the risk of handling errors as well as radiological injuries. Hence, there is potential for automated injection devices to replace manual injection methods. In this study, the effect of micro-bolus pulse injection technology was compared and verified by radioactive experiments using a programmable injection pump, and the overall bubble recognition experiment and rat tail vein simulation injection verification were performed using the piezoelectric sensor preloading method. The results showed that at the same injection peak speed, the effective flushing volume of micro-bolus pulse flushing (about 83 μL/pulse) was 49.65% lower than that of uniform injection and 25.77% lower than that of manual flushing. In order to avoid the dilution effect of long pipe on the volume of liquid, the use of piezoelectric sensor for sealing preloading detection could accurately predict the bubbles of more than 100 μL in the syringe. In the simulated injection experiment of rat tail vein, when the needle was placed in different tissues by preloading 100 μL normal saline, the piezoelectric sensor fed back a large difference in pressure attenuation rate within one second, which was 2.78% in muscle, 17.28% in subcutaneous and 54.71% in vein. Micro-bolus pulse injection method and piezoelectric sensor sealing preloading method have application potential in improving the safety of radiopharmaceutical automatic bolus injection.