Dynamics of a living body enables organs to experience mechanical stimulation at cellular level. Human cardiomyocytes cell line provides a source for simulating the heart dynamics; however, lack of ...understanding on mechanical stimulation effect on them limits potential applications. Here, we investigated the effect of mechanical stimulation on the cardiac function‐associated protein expressions in human cardiomyocytes. Human cardiomyocyte cell line AC16 was subjected to different stresses: 5% mild and 25% aggressive, at 1Hz for 24h. The stretched cardiomyocytes showed down‐regulated Piezo1, P‐AKTS473, and P‐GSK3bS9 compared to no stretch. In addition, the stretched cardiomyocytes showed increased LRP6, and P‐JNKT183/T185. When Piezo inhibitor was added to the cells during stretching, the LRP6, and P‐JNKT183/T185 were further increased under 25%, but not 5%, suggesting that higher mechanical stress further activated the Wnt‐related signaling pathway when Piezo1 was inhibited. Supporting this idea, we found expression of eNOS decreased, and release of calcium ions significantly reduced under 25% compared to 5%. These studies demonstrate that cyclic mechanical stimulation affects cardiac function‐associated protein expressions, and Piezo1 plays a role in the protein regulation.
Support or Funding Information
This research is supported by VGHKS107‐076, VGHKS107‐168, VGHKS107‐175, MOST104‐2320‐B‐0751B‐003‐MY3, and MOST106‐2320‐B‐075B‐001.
This is from the Experimental Biology 2019 Meeting. There is no full text article associated with this published in The FASEB Journal.
Plants are subjected to a multitude of stimuli during insect herbivory, resulting in a complex and cumulative defence response. Breaking down the components of herbivory into specific stimuli and ...identifying the mechanisms of defence associated with them has thus far been challenging. Advances in our understanding of responses to inconspicuous stimuli, such as those induced by microbial symbionts in herbivore secretions and mechanical stimulation caused by insects, have illuminated the intricacies of herbivory. Here, we provide a synthesis of the interacting impacts of herbivory on plants and the consequential complexities associated with uncoupling defence responses. We propose that simulated herbivory should be used to complement true herbivory to decipher the mechanisms of insect herbivore-induced plant defence responses.
Ground-breaking research into the chemical and biochemical signals of plant defences has dramatically increased our capacity to understand many of the details that underpin plant–herbivore ecology.
Herbivore-associated microbes, chemical elicitation, and mechanical stimulation are all known to activate diverse signalling pathways.
True herbivory can be useful to obtain information on the collective plant response, but it cannot disassociate mechanistic responses of specific defence pathways triggered by the different stimuli associated with herbivore feeding.
Simulating the chemical and physical factors associated with herbivory in isolation will allow us to disassemble plant defence responses and understand which stimuli are associated with a given defence response.
Introduction
One of the key limitations of distraction osteogenesis (DO) is the absence or delayed formation of a callus in the distraction gap, which can ultimately prolong the duration of ...treatment.
Purpose
Multiple modalities of distraction regenerate (DR) stimulation are reviewed, with a focus on modulation of the mechanical environment required for DR formation and maturation.
Methods
Preparing the review, the scientific platforms such as PubMed, Scopus, ResearchGate, RSCI were used for information searching. Search words or word combinations were mechanical bone union stimulation; axial dynamization, distraction regenerate.
Results
Recent advances in mechanobiology prove the effectiveness of axial loading and mechanical stimulation during fracture healing. Further investigation is still required to develop the proper protocols and applications for invasive and non-invasive stimulation of the DR. Understanding the role of dynamization as a mechanical stimulation method is impossible without a consensus on the use of the terms and protocols involved.
Discussion
We propose to define Axial Dynamization as the ability to provide axial load at the bone regeneration site with minimal translation and bending strain. Axial Dynamization works and is most likely achieved through multiple mechanisms: direct stimulation of the tissues by axial cyclic strain and elimination of translation forces at the DR site by reducing the effects of the cantilever bending of the pins.
Conclusion
Axial Dynamization, along with other non-invasive methods of mechanical DR stimulation, should become a default component of limb-lengthening protocols.
Due to the lack of blood and nutrition supply, the repairing of cartilage defect has become a challenging topic in clinical treatment. Herein, a unique porous scaffold based on regenerated silk ...fibroin (RSF) was fabricated by using freeze-drying after enzymatical crosslinking. Results showed that the pore size, mechanical properties and cytocompatibility of the scaffold were all significantly improved by proper combination of bacterial cellulose nanofiber ribbon (BCNR), thus much appropriate for cartilage regeneration. Based on this RSF/BCNR composite scaffold, the effects of stair-stepping shaped dynamic hydrostatic pressure (DHP) on the construction of tissue engineered cartilage in vitro and dynamic loading microenvironment on the regeneration of cartilage defect in vivo have been comprehensively investigated for the first time. Compared with traditional static culture, DHP has obviously enhancing chondrocyte growth and cartilage specific matrix deposition. Compared with the unloading microenvironment in vivo, corresponding dynamic loading microenvironment significantly improved cartilage regeneration, as it presented apparent cartilage lacuna like structure and thicker newly formed cartilage tissue. The insights of in vitro and in vivo dynamic mechanical stimulations enhancing effects on cartilage regeneration based on the RSF/BCNR composite scaffold revealed in this study could provide valuable guidance for the construction of optimal tissue engineered cartilage and the clinical prevention and treatment of orthopedic diseases.
Display omitted
•A unique RSF/BCNR composite scaffold with improved pore size, mechanical strength and cytocompatibility was fabricated.•Effects of dynamic mechanical stimulations on the in vitro and in vivo cartilage regeneration have been comprehensively investigated.•Dynamic mechanical stimulations have significantly improved cartilage regeneration based on the RSF/BCNR scaffold.
The field of cardiac tissue engineering has made significant strides over the last few decades, highlighted by the development of human cell derived constructs that have shown increasing functional ...maturity over time, particularly using bioreactor systems to stimulate the constructs. However, the functionality of these tissues is still unable to match that of native cardiac tissue and many of the stem-cell derived cardiomyocytes display an immature, fetal like phenotype. In this review, we seek to elucidate the biological underpinnings of both mechanical and electrical signaling, as identified via studies related to cardiac development and those related to an evaluation of cardiac disease progression. Next, we review the different types of bioreactors developed to individually deliver electrical and mechanical stimulation to cardiomyocytes in vitro in both two and three-dimensional tissue platforms. Reactors and culture conditions that promote functional cardiomyogenesis in vitro are also highlighted. We then cover the more recent work in the development of bioreactors that combine electrical and mechanical stimulation in order to mimic the complex signaling environment present in vivo. We conclude by offering our impressions on the important next steps for physiologically relevant mechanical and electrical stimulation of cardiac cells and engineered tissue in vitro.
Display omitted
Osteocytes function as critical regulators of bone homeostasis by coordinating the functions of osteoblasts and osteoclasts, and are constantly exposed to mechanical force. However, the molecular ...mechanism underlying the mechanical signal transduction in osteocytes is not well understood. Here, we found that Yoda1, a selective Piezo1 agonist, increased intracellular calcium mobilization and dose-dependently decreased the expression of Sost (encoding Sclerostin) in the osteocytic cell line IDG-SW3. We also demonstrated that mechanical stretch of IDG-SW3 suppressed Sost expression, a result which was abrogated by treatment with the Piezo1 inhibitor GsMTx4, and the deficiency of Piezo1. Furthermore, the suppression of Sost expression was abolished by treatment with an Akt inhibitor. Taken together, these results indicate that the activation of the Piezo1-Akt pathway in osteocytes is required for mechanical stretch-induced downregulation of Sost expression.
•Osteocytic IDG-SW3 cells express functional Piezo1.•A Piezo1 agonist Yoda1 suppresses Sost expression in osteocytic IDG-SW3 cells.•Mechanically stretched osteocytic IDG-SW3 cells exhibit decreased Sost expression.•Sost suppression is completely abrogated by the deficiency of Piezo1.•Mechanical stretch induces Sost suppression via Piezo1-Akt pathway in osteocytes.
Body tissues are exposed to a complex mechanical environment, which is perceived by cells and converted to biochemical signals such as ATP release. We performed a meta-analysis of 278 systematically ...identified studies that investigated mechanically stimulated ATP release (MSAR) to quantify the amounts, kinetics and mechanisms of ATP release under normal and pathological conditions. Mechanically stimulated mammalian cells were shown to release 38.6 95% confidence interval (CI): 18.2-81.8 amol ATP/cell on average with a characteristic time constant of 32 s (95% CI: 16-66). Analysis of ATP release mechanisms revealed the existence of conserved and tissue-specific release routes. We assessed ATP release in pathophysiological states, and found that ATP release was elevated in inflammation and injury, and attenuated in hereditary (such as cystic fibrosis) and metabolic (such as type II diabetes) conditions. Our study links cell-specific ATP release mechanisms to pathophysiological changes in ATP release and allows ATP release-targeting interventions to be mapped to site-specific effects. This work demonstrates that quantitative synthesis of basic research can generate non-trivial hypotheses and inform evidence-driven translational studies.
Transfection
In article number 2103198, Andy Tay and Nicholas Melosh illustrate the use of high aspect‐ratio hollow nanostructures coupled with transient electroporation for electrophoretic delivery ...of DNA into T cell. Magnetic stimulation was added subsequently to enhance intracellular DNA transport towards the nucleus to achieve high transfection efficiency. Facilitated by magnetic manipulation, the whole gene delivery process is centrifuge‐free, making it compatible with end‐to‐end cell manufacturing.
Secondary bone healing requires an adequate level of mechanical stimulation expressed by the extent of interfragmentary motion in the fracture. However, there is no consensus about when the ...mechanical stimulation should be initiated to ensure a timely healing response. Therefore, this study aims to compare the effect of the immediate and delayed application of mechanical stimulation in a large animal model.
Twelve Swiss White Alpine sheep underwent partial osteotomy of a tibia that was stabilised with an active fixator inducing well-controlled mechanical stimulation. Animals were randomly assigned into two groups with different stimulation protocols. The immediate group received daily stimulation (1000 cycles/day) from the first day post-operation, while in the delayed group, stimulation began only on the 22nd day post-operation. Healing progression was evaluated daily by measuring the in vivo stiffness of the repair tissue and by quantifying callus area on weekly radiographs. All animals were euthanised five weeks post-op. Post-mortem callus volume was determined from high-resolution computer tomography (HRCT).
Fracture stiffness (p < 0.05) and callus area (p < 0.01) were significantly larger for the immediate group compared to the delayed stimulation group. In addition, the callus volume measured on the post-mortem HRCT showed 319 % greater callus volume for the immediate stimulation group (p < 0.01).
This study demonstrates that a delay in the onset of mechanical stimulation retards fracture callus development and that mechanical stimulation already applied in the early post-op phase promotes bone healing.
•A sheep tibia osteotomy was instrumented with an active external fixator.•The fixator introduces well-controlled mechanical stimulation in the osteotomy.•The model was used to compare the effect of immediate vs delayed stimulation.•Immediate stimulation accelerates bone healing in comparison to delayed stimulation.
PDF
