Compressive Mechanical Loading Research Articles

Deletion of vitamin D receptor exacerbated temporomandibular joint pathological changes under abnormal mechanical stimulation

AimsTemporomandibular disorder can cause degenerative pathological changes by aseptic inflammation in the temporomandibular joint (TMJ). Vitamin D (VD) is known for maintaining calcium homeostasis, and recent studies indicated that VD and the vitamin D receptor (VDR) are important in inflammatory responses. In this study, we explored the anti-inflammatory effect of VD-VDR signaling axis in TMJ pathological degeneration. Main methodsMice ablated for Vdr (Vdr−/−res) were fed with a rescue diet to avoid hypocalcemia. With abnormal mechanical stimulation, unilateral anterior crossbite (UAC) induced temporomandibular disorders in mice. Histological staining, immunohistochemistry staining, and micro-CT analysis were performed to evaluate TMJ pathological changes. To identify the mechanisms in the aseptic inflammatory process, in vitro experiments were conducted on wild-type (WT) and Vdr−/− chondrocytes with compressive mechanical stress loading, and the related inflammatory markers were examined. Key findingsVdr−/−res mice did not develop rickets with a high calcium rescue diet. The TMJ cartilage thickness in Vdr−/−res mice was significantly decreased with mechanical stress stimulation compared to WT mice. UAC-induced bone resorption was obvious, and the number of osteoclasts significantly increased in Vdr−/−res mice. The proliferation was inhibited and the gene expression of Il1b, Mmp3, and Mmp13 was significantly increased in Vdr−/− chondrocytes. However, WT chondrocytes showed significantly increased Tnfa gene expression as a response to mechanical stress but not in Vdr−/− chondrocytes. SignificanceVD-VDR is crucial in TMJ pathological changes under abnormal mechanical stimulation. Deletion of Vdr exacerbated inflammatory response excluding TNFα, inhibited chondrocyte proliferation, and promoted bone resorption in TMJ.

A 3D bioreactor model to study osteocyte differentiation and mechanobiology under perfusion and compressive mechanical loading

Osteocytes perceive and process mechanical stimuli in the lacuno-canalicular network in bone. As a result, they secrete signaling molecules that mediate bone formation and resorption. To date, few three-dimensional (3D) models exist to study the response of mature osteocytes to biophysical stimuli that mimic fluid shear stress and substrate strain in a mineralized, biomimetic bone-like environment. Here we established a biomimetic 3D bone model by utilizing a state-of-art perfusion bioreactor platform where immortomouse/Dmp1-GFP-derived osteoblastic IDG-SW3 cells were differentiated into mature osteocytes. We evaluated proliferation and differentiation properties of the cells on 3D microporous scaffolds of decellularized bone (dBone), poly(L-lactide-co-trimethylene carbonate) lactide (LTMC), and beta-tricalcium phosphate (β-TCP) under physiological fluid flow conditions over 21 days. Osteocyte viability and proliferation were similar on the scaffolds with equal distribution of IDG-SW3 cells on dBone and LTMC scaffolds. After seven days, the differentiation marker alkaline phosphatase (Alpl), dentin matrix acidic phosphoprotein 1 (Dmp1), and sclerostin (Sost) were significantly upregulated in IDG-SW3 cells (p = 0.05) on LTMC scaffolds under fluid flow conditions at 1.7 ml/min, indicating rapid and efficient maturation into osteocytes. Osteocytes responded by inducing the mechanoresponsive genes FBJ osteosarcoma oncogene (Fos) and prostaglandin-endoperoxide synthase 2 (Ptgs2) under perfusion and dynamic compressive loading at 1 Hz with 5 % strain. Together, we successfully created a 3D biomimetic platform as a robust tool to evaluate osteocyte differentiation and mechanobiology in vitro while recapitulating in vivo mechanical cues such as fluid flow within the lacuno-canalicular network. Statement of significanceThis study highlights the importance of creating a three-dimensional (3D) in vitro model to study osteocyte differentiation and mechanobiology, as cellular functions are limited in two-dimensional (2D) models lacking in vivo tissue organization. By using a perfusion bioreactor platform, physiological conditions of fluid flow and compressive loading were mimicked to which osteocytes are exposed in vivo. Microporous poly(L-lactide-co-trimethylene carbonate) lactide (LTMC) scaffolds in 3D are identified as a valuable tool to create a favorable environment for osteocyte differentiation and to enable mechanical stimulation of osteocytes by perfusion and compressive loading. The LTMC platform imitates the mechanical bone environment of osteocytes, allowing the analysis of the interaction with other cell types in bone under in vivo biophysical stimuli.

Stress-induced phase stability and optoelectronic property changes in cesium lead halide perovskites

Over the past decade, the certified power conversion efficiency of perovskite solar cells (PSCs) has increased to 26.1%. However, phase instability originating from lattice strains, has limited their commercialization. Strains will inevitably be generated during the PSC fabrication and service process due to the “soft lattice” nature of halide perovskites. In particular, flexible PSCs are subjected to not only mechanical tensile and compressive loads, but also suffer from thermal stresses. In this study, strain-induced changes in the phase stability and the corresponding optoelectronic properties of CsPbI3−xBrx (CsPbI3, CsPbBr3, and CsPbI2Br) systems under tensile and compressive stresses were investigated using first-principles calculations. The results showed that compressive stresses reduce the bandgap value and increase the light absorption coefficient; thus, the optoelectronic performance is improved, whereas the light absorption coefficient decreases regardless of how the bandgap changes under tensile stresses. Moreover, under the same stress, the tensile strain value was twice that of the compressive strain, and the critical value of the transition from the cubic to tetragonal phase was lower, indicating that phase stability was worse under tensile stresses. Therefore, during the fabrication of PSCs, the tensile stress state should be adjusted to the compressive stress state, which is favorable for enhancing PSCs photovoltaic performance and phase stability. The results not only provide direct evidence of tensile and compressive strains influencing the phase stability and optoelectronic property changes in halide perovskites, but also highlight lattice-strain tailoring for the composition design, process optimization, and interface engineering of efficient and stable PSCs.

Nonlinear dynamic stability analysis of CNTs reinforced piezoelectric viscoelastic composite nano/micro plate under multiple physical fields resting on smart foundation

This study analyzes the nonlinear dynamic stability of carbon nanotube reinforced composite (CNTRC) piezoelectric viscoelastic nano/micro plate under time dependent harmonic compressive biaxial mechanical loading. The nano/micro plate is single-layer with a uniform and rectangular cross section. Polyvinylidene fluoride (PVDF) is the material used for the nano/micro plate. Also, it is located on a nonlinear viscoelastic piezoelectric foundation made of Zinc Oxide (ZnO). Single-walled carbon nanotubes (SWCNTs) have been used to strengthen nano/micro plate. Using Kelvin-Voigt model, the material properties of the system are assumed to be viscoelastic. Nano/micro plate is subjected to 2D magnetic field and electric potential. Magnetic field effects are incorporated using Maxwell’s relations. An alternating and direct voltage is applied to the nano/micro plate and also smart foundation in thickness direction. Eshelby-Mori-Tanaka approach is used to estimate the effective elastic properties. Additionally, follower force and uniform thermal gradient is applied to nano/micro plate in this study. The nonlinear strain–displacement relations are based on the Von-Kármán theory. According to classical, first order, third order, sinusoidal, parabolic, hyperbolic and exponential shear deformation plate theories, a new formulation is proposed incorporating surface stress effects through the Gurtin-Murdoch elasticity theory. In order to consider small scale parameters, this research is based on modified strain gradient theory (MSGT). Using the energy method and Hamilton’s principle, the non classical governing equations are derived. For nano/micro plate, simply supported boundary conditions are considered. For the purpose of solving differential equations, an analysis based on Galerkin procedure and finally the Bolotin method will be used to obtain the dynamic instability region (DIR). It is the objective of this study to investigate the impact of such parameters as small-scale parameters, alternating and direct applied voltage, intensity of magnetic field, surface effects, thermal environment and static load factor on the DIR. This study revealed that taking into account the smart foundation reduces the area of dynamic instability region by more than 60% for a constant intensity of magnetic field. The stability responses are also more convergent with the smart foundation. Additionally, the range is moved toward higher excitation frequencies and greater system stability. Validation of answers based on reliable scientific articles is one of the final stages of this research. These results can be used to design nano/micro electromechanical systems.

Effect of simultaneous electrical and mechanical stressing on porosity of Ti3C2T x MXene films

MXenes are atomically layered carbides and nitrides of transition metals that have potential for micro-devices applications in energy storage, conversion, and transport. This emerging family of materials is typically studied as nanosheets or ultra-thin films, for which the internal defects are mostly nanoscale flake-flake interface separation type. However, micro-devices applications would require thicker films, which exhibit very high density of microscale pores. Electrical conductivity of thicker MXenes is significantly lower than nanosheets, and the physics of defect size and density control are also different and less understood. Current art is to perform high temperature annealing to improve the electrical conductivity, which can structurally alter or degrade MXene. The key contribution of this study is a room-temperature annealing process that exploits the synergy between electrical pulses and compressive mechanical loading. Experimental results indicate over a 90% increase in electrical conductivity, which reflects a decrease in void size and density. In the absence of compressive loading, the same process resulted in a conductivity increase of approximately 75%. Analytical spectroscopy and microscopy indicated that the proposed multi-stimuli process kept the MXene composition intact while significantly decreasing the void size and density.

Generalized modeling and experimental research on the transient response of supercapacitors under compressive mechanical loads

Generalized modeling and experimental research on the transient response of supercapacitors under compressive mechanical loads

Correlation of Acoustic Emissions with Electrical Signals in the Vicinity of Fracture in Cement Mortars Subjected to Uniaxial Compressive Loading

Acoustic emissions (AEs) and weak electrical signals, also known as pressure stimulated currents (PSCs), were concurrently recorded in order to investigate their behavior and detect precursory indicators when cement mortar specimens were subjected to mechanical compressive loading, emphasizing the behavior of the AEs and the PSC signal in the vicinity of fracture. The axial compressive loading protocol incorporated a constantly increasing stress, from early stress values up to the vicinity of fracture and a sequential stress stabilization until the time the specimen collapses, due to severe growing internal damages. Concurrent recordings of the electrical and acoustic emissions were performed. The AE recordings were analyzed, by incorporating the recently introduced F- and P-functions, and the well-known b-value. The experimental results highlight strong similarities regarding the variations of the PSC signal, the AE hits occurrence rate (F-function), and the AE hits energy release rate (P-function). The above was also confirmed with another similar experiment in an identical specimen. It is noteworthy that, during the stay of the specimens under a constant load regime near their strength levels, a peak appears in the above quantities, which is directly related to an increased rate of axial deformation. The temporal evolution of the b-values is also presented. Results show that the local minima appearing at values close to b ≈ 1.0 correspond to the local maxima of the PSC signal. It is straightforwardly concluded that when both the PSC signal and the AE data are combined, they provide clear pre-failure indicators.

ZAKβ is activated by cellular compression and mediates contraction‐induced MAP kinase signaling in skeletal muscle

Mechanical inputs give rise to p38 and JNK activation, which mediate adaptive physiological responses in various tissues. In skeletal muscle, contraction‐induced p38 and JNK signaling ensure adaptation to exercise, muscle repair, and hypertrophy. However, the mechanisms by which muscle fibers sense mechanical load to activate this signaling have remained elusive. Here, we show that the upstream MAP3K ZAKβ is activated by cellular compression induced by osmotic shock and cyclic compression in vitro, and muscle contraction in vivo. This function relies on ZAKβ's ability to recognize stress fibers in cells and Z‐discs in muscle fibers when mechanically perturbed. Consequently, ZAK‐deficient mice present with skeletal muscle defects characterized by fibers with centralized nuclei and progressive adaptation towards a slower myosin profile. Our results highlight how cells in general respond to mechanical compressive load and how mechanical forces generated during muscle contraction are translated into MAP kinase signaling.

A Novel Ex Vivo Bone Culture Model for Regulation of Collagen/Apatite Preferential Orientation by Mechanical Loading.

The anisotropic microstructure of bone, composed of collagen fibers and biological apatite crystallites, is an important determinant of its mechanical properties. Recent studies have revealed that the preferential orientation of collagen/apatite composites is closely related to the direction and magnitude of in vivo principal stress. However, the mechanism of alteration in the collagen/apatite microstructure to adapt to the mechanical environment remains unclear. In this study, we established a novel ex vivo bone culture system using embryonic mouse femurs, which enabled artificial control of the mechanical environment. The mineralized femur length significantly increased following cultivation; uniaxial mechanical loading promoted chondrocyte hypertrophy in the growth plates of embryonic mouse femurs. Compressive mechanical loading using the ex vivo bone culture system induced a higher anisotropic microstructure than that observed in the unloaded femur. Osteocytes in the anisotropic bone microstructure were elongated and aligned along the long axis of the femur, which corresponded to the principal loading direction. The ex vivo uniaxial mechanical loading successfully induced the formation of an oriented collagen/apatite microstructure via osteocyte mechano-sensation in a manner quite similar to the in vivo environment.

Piezoresistive 3D graphene–PDMS spongy pressure sensors for IoT enabled wearables and smart products

Recently, 3D porous graphene–polymer composite-based piezoresistive sensors have gained significant traction in the field of flexible electronics owing to their ultralightweight nature, high compressability, robustness, and excellent electromechanical properties. In this work, we present an improved facile recipe for developing repeatable, reliable, and linear 3D graphene–polydimethylsiloxane (PDMS) spongy sensors for internet of things (IoT)-enabled wearable systems and smart consumer products. Fundamental morphological characterization and sensing performance assessment of the piezoresistive 3D graphene–polymer sensor were conducted to establish its suitability for the development of squeezable, flexible, and skin-mountable human motion sensors. The density and porosity of the sponges were determined to be 250 mg cm−3 and 74% respectively. Mechanical compressive loading tests conducted on the sensors revealed an average elastic modulus as low as ∼56.7 kPa. Dynamic compressive force-resistance change response tests conducted on four identical sensors revealed a linear piezoresistive response (in the compressive load range 0.42–2.18 N) with an average force sensitivity of 0.3470 ± 0.0794 N−1. In addition, an accelerated lifetime test comprising 1500 compressive loading cycles (at 3.90 N uniaxial compressive loading) was conducted to demonstrate the long-term reliability and stability of the sensor. To test the applicability of the sensors in smart wearables, four identical graphene–PDMS sponges were configured on the fingertip regions of a soft nitrile glove to develop a pressure sensing smart glove for real-time haptic pressure monitoring. Similarly, the sensors were also integrated into the Philips 9000 series electric shaver to realize smart shaving applications with the ability to monitor shaving motions. Furthermore, the readiness of our system for next-generation IoT-enabled applications was demonstrated by integrating the smart glove with an embedded system software utilizing the an open source microcontroller platform. The system was capable of identifying real-time qualitative pressure distribution across the fingertips while grasping daily life objects, thus establishing the suitability of such sensors for next-generation wearables for prosthetics, consumer devices, and personalized healthcare monitoring devices.

WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues.

SummaryWhen crawling through the body, leukocytes often traverse tissues that are densely packed with extracellular matrix and other cells, and this raises the question: How do leukocytes overcome compressive mechanical loads? Here, we show that the actin cortex of leukocytes is mechanoresponsive and that this responsiveness requires neither force sensing via the nucleus nor adhesive interactions with a substrate. Upon global compression of the cell body as well as local indentation of the plasma membrane, Wiskott-Aldrich syndrome protein (WASp) assembles into dot-like structures, providing activation platforms for Arp2/3 nucleated actin patches. These patches locally push against the external load, which can be obstructing collagen fibers or other cells, and thereby create space to facilitate forward locomotion. We show in vitro and in vivo that this WASp function is rate limiting for ameboid leukocyte migration in dense but not in loose environments and is required for trafficking through diverse tissues such as skin and lymph nodes.

Hemodynamic stress shapes subchondral bone in osteoarthritis: An emerging hypothesis.

Osteoarthritis (OA) is no longer regarded as a simple wear-and-tear problem of articular cartilage. Instead, OA is a whole joint disorder involving both cartilaginous and non-cartilaginous tissues such as subchondral bone and synovium. Among them, subchondral bone undergoes constant remodeling in response to the changes of mechanical environment. Current understanding of subchondral bone disturbance in OA is limited to its link with an altered local mechanical loading as a result of ligament or meniscus injury. Very recently, hypertension, the most common vascular morbidity, has been emerged as an independent risk factor of OA. It might suggest a plausible role of systemic hemodynamic mechanical stress in subchondral bone remodeling and the pathogenesis of OA. However, their relationship remains not fully understood. Based on our preliminary clinical observation on the association of hemodynamic parameters with subchondral bone mass and microstructure in late-stage knee OA patients, we formulate a vascular etiology hypothesis of OA from a mechanobiology perspective. Noteworthily, hemodynamic stress associated with subchondral bone mineral density; yet compressive mechanical loading does not. Furthermore, hemodynamic parameters positively correlated with subchondral plate-like trabecular bone volume but negatively associated with rod-like trabecular bone volume. In contrast, compressive mechanical loading tends to increase both plate-like and rod-like trabecular bone volume. Taken together, it warrants further investigations into the distinct role of hemodynamic or compressive stress in shaping subchondral bone in the pathophysiology of OA.The Translational potential of this articleThis work provides a new insight, from the angle of biomechanics, into the emerging role of vascular pathologies, such as hypertension, in the pathogenesis of OA. It might open up a new avenue for the development of a mechanism-based discovery of novel diagnostics and therapeutics.

Investigation of self-heating and dissipative effects in ferroelectric ceramics subjected to compressive mechanical cyclic loading

In this study the behavior of a soft PZT ceramic subjected to compressive cyclic loadings is investigated with the aim of providing an insight into different dissipative processes which affect the ferroelastic cyclic behavior of the material. Two quantitative imaging techniques, infrared (IR) thermography and digital image correlation (DIC), are employed to measure superficial temperature and in-plane displacement of the sample under mechanical cyclic loadings. Thermal and strain responses are further deduced from these measurements. This allows to quantify the energy dissipated by the material during applied mechanical loadings. Self-heating (SH) and DIC measurements reveal that, even in the piezoelectric regime, the level of dissipation is significant. This suggests that PZT ceramic response under cyclic compression is significantly influenced by domain switching mechanisms. The two imaging techniques are shown to be efficient tools to identify domain wall activity in ferroelectric ceramics and can be advantageously substituted for polarization measurements when polarization variations are too small to be detected. It is also shown that, due to the initial compressive stress experienced by all specimens, the domain wall activity under cyclic uniaxial compressive stress is almost independent of the initial polarization state of the material.

Physiologic Mechanical Stress Directly Induces Bone Formation by Activating Glucose Transporter 1 (Glut 1) in Osteoblasts, Inducing Signaling via NAD+-Dependent Deacetylase (Sirtuin 1) and Runt-Related Transcription Factor 2 (Runx2).

Mechanical stress is an important factor affecting bone tissue homeostasis. We focused on the interactions among mechanical stress, glucose uptake via glucose transporter 1 (Glut1), and the cellular energy sensor sirtuin 1 (SIRT1) in osteoblast energy metabolism, since it has been recognized that SIRT1, an NAD+-dependent deacetylase, may function as a master regulator of the mechanical stress response as well as of cellular energy metabolism (glucose metabolism). In addition, it has already been demonstrated that SIRT1 regulates the activity of the osteogenic transcription factor runt-related transcription factor 2 (Runx2). The effects of mechanical loading on cellular activities and the expressions of Glut1, SIRT1, and Runx2 were evaluated in osteoblasts and chondrocytes in a 3D cell–collagen sponge construct. Compressive mechanical loading increased osteoblast activity. Mechanical loading also significantly increased the expression of Glut1, significantly decreased the expression of SIRT1, and significantly increased the expression of Runx2 in osteoblasts in comparison with non-loaded osteoblasts. Incubation with a Glut1 inhibitor blocked mechanical stress-induced changes in SIRT1 and Runx2 in osteoblasts. In contrast with osteoblasts, the expressions of Glut1, SIRT1, and Runx2 in chondrocytes were not affected by loading. Our present study indicated that mechanical stress induced the upregulation of Glut1 following the downregulation of SIRT1 and the upregulation of Runx2 in osteoblasts but not in chondrocytes. Since SIRT1 is known to negatively regulate Runx2 activity, a mechanical stress-induced downregulation of SIRT1 may lead to the upregulation of Runx2, resulting in osteoblast differentiation. Incubation with a Glut1 inhibitor the blocked mechanical stress-induced downregulation of SIRT1 following the upregulation of Runx2, suggesting that Glut1 is necessary to mediate the responses of SIRT1 and Runx2 to mechanical loading in osteoblasts.

Differential behaviour and gene expression in 3D cultures of femoral- and calvarial-derived human osteoblasts under a cyclic compressive mechanical load.

The aim of the study was to compare the response of calvarial and femoral osteoblasts cultured in a 3D hydrogel environment to cyclic compressive mechanical loading. Human foetal femoral and calvarial osteoblasts were encapsulated in a semi-synthetic thiol-modified hyaluronan gelatin polyethylene glycol diacrylate (PEGDA) cross-linked HyStemC hydrogel. Constructs were subjected to a cyclic compressive strain of 33.4kPa force every second for 5 s every hour for 6 h per day using FlexCell BioPress culture plates and compared to non-compressed constructs. Cell viability, mineralisation, and morphological changes were observed over 21 days. BMP2, ALP, COL1A1, COL2A1, and OCN gene expression levels were quantified. Encapsulated osteoblast numbers increased and formed hydroxyapatite over a 21-day period. Cell viability decreased under a cyclical strain when compared to cells under no strain. Femoral osteoblasts under strain expressed increased levels of BMP2 (53.9-fold) and COL1A1 (5.1-fold) mRNA compared to no strain constructs. Surprisingly, no BMP2 mRNA was detected in calvarial osteoblasts. Osteoblasts derived from endochondral (femoral) and intra-membranous (calvarial) processes behaved differently in 3D-constructs. We therefore recommend that site-specific osteoblasts be used for future bone engineering and bone replacement materials and further research undertaken to elucidate how site-specific osteoblasts respond to cyclic compressive loads.

Boundary influence on the fields and arrangement of the needle domains in barium titanate single crystals

The superposition theory is adopted to study the boundary value problem of needle domains in barium titanate single crystals, which decomposes into an infinite-medium solution and a complementary solution. The model of an equivalent edge dislocation and line charge is adopted to calculate the fields due to the discrete needle domains in an infinite medium. The complementary solutions are obtained from a linear elastic boundary value problem using the finite element method. The influence of boundaries on the fields and arrangement of the needles in thin barium titanate single crystals is analysed, by considering traction-free boundaries and using the plane stress approximation. According to the principle of minimum potential energy, it is found that pairs of parallel needle domains can be stabilized if the effective charge associated with the needle tips is reduced to 48% of the material’s full polarization charge. The evolution of comb-like arrays of needle domains under compressive mechanical load is simulated, and the results are found to be qualitatively similar to experimental observations which have not previously been explained theoretically.

Intra-articular injection of phospholipid-based lubricant reduces shear-responsive inflammatory genes in the superficial layer of cartilage post murine joint destabilisation

Purpose: The synovial joint exhibits extraordinary biotribological properties allowing the articular cartilage layers to slide past each other at very low friction even under local pressures of up to 18 MPa (∼180 atm). Articular cartilage is exquisitely mechanical sensitive. Compressive mechanical load contributes to articular cartilage homeostasis; however, overuse or destabilizing the joint increases surface shear stress, which promotes cartilage degradation. Our previous Results show that shear stress, induced by joint destabilization, regulates a number of inflammatory genes 6h post surgery, including Mmp3, Il1b, Arg1, Ccl2, and Il6.

Compressive mechanical stress enhances susceptibility to interleukin-1 by increasing interleukin-1 receptor expression in 3D-cultured ATDC5 cells

BackgroundMechanical overload applied on the articular cartilage may play an important role in the pathogenesis of osteoarthritis. However, the mechanism of chondrocyte mechanotransduction is not fully understood. The purpose of this study was to assess the effects of compressive mechanical stress on interleukin-1 receptor (IL-1R) and matrix-degrading enzyme expression by three-dimensional (3D) cultured ATDC5 cells. In addition, the implications of transient receptor potential vanilloid 4 (TRPV4) channel regulation in promoting effects of compressive mechanical loading were elucidated.MethodsATDC5 cells were cultured in alginate beads with the growth medium containing insulin-transferrin-selenium and BMP-2 for 6 days. The cultured cell pellet was seeded in collagen scaffolds to produce 3D-cultured constructs. Cyclic compressive loading was applied on the 3D-cultured constructs at 0.5 Hz for 3 h. The mRNA expressions of a disintegrin and metalloproteinases with thrombospondin motifs 4 (ADAMTS4) and IL-1R were determined with or without compressive loading, and effects of TRPV4 agonist/antagonist on mRNA expressions were examined. Immunoreactivities of reactive oxygen species (ROS), TRPV4 and IL-1R were assessed in 3D-cultured ATDC5 cells.ResultsIn 3D-cultured ATDC5 cells, ROS was induced by cyclic compressive loading stress. The mRNA expression levels of ADAMTS4 and IL-1R were increased by cyclic compressive loading, which was mostly prevented by pyrollidine dithiocarbamate. Small amounts of IL-1β upregulated ADAMTS4 and IL-1R mRNA expressions only when combined with compressive loading. TRPV4 agonist suppressed ADAMTS4 and IL-1R mRNA levels induced by the compressive loading, whereas TRPV4 antagonist enhanced these levels. Immunoreactivities to TRPV4 and IL-1R significantly increased in constructs with cyclic compressive loading.ConclusionCyclic compressive loading induced mRNA expressions of ADAMTS4 and IL-1R through reactive oxygen species. TRPV4 regulated these mRNA expressions, but excessive compressive loading may impair TRPV4 regulation. These findings suggested that TRPV4 regulates the expression level of IL-1R and subsequent IL-1 signaling induced by cyclic compressive loading and participates in cartilage homeostasis.

Axial magnetic field effect on wave propagation in bi-layer FG graphene platelet-reinforced nanobeams

This paper aims to investigate the size-dependent wave propagation in functionally graded (FG) graphene platelet (GPL)-reinforced composite bi-layer nanobeams embedded in Pasternak elastic foundation and exposed to in-plane compressive mechanical load and in-plane magnetic field. The small-scale effects are taken into account by employing the nonlocal strain gradient theory that contains two different length scale parameters. The present two nanobeams are made of multi-composite layers. Each layer is composed of a polymer matrix reinforced by uniformly distributed and randomly oriented GPLs. The GPLs weight fraction is graded from layer to other according to a new piece-wise rule and then four distribution types will be established. Our technique depends on applying the four-variable shear and normal deformations theory to model the wave propagation problem. The equations of motion are obtained using Hamilton principle. These equations are then analytically solved to obtain the wave frequencies and phase velocities of the waves. The calculated results are compared with those published in the literature. The impacts of the length scale parameters, foundation stiffness, in-plane magnetic field, weight fraction of graphene, graphene platelets distribution type and beam geometry on the propagating waves in the FG GPLs nanobeams are discussed in details. It is found that the strength of the composite beams may be enhanced with increasing in the GPLs weight fraction and magnetic field leading to an increment in the phase velocity and wave frequency of the present system.

Cyclic compressive mechanical loading on three­dimensional cultured tissue of human chondrocytes synergistically upregulates MMP­-3 gene expression with IL­-1β

Cyclic compressive mechanical loading on three­dimensional cultured tissue of human chondrocytes synergistically upregulates MMP­-3 gene expression with IL­-1<i>β </i>