Bone undergoes a constant reconstruction process of resorption and formation called bone remodeling, so that it can endure mechanical loading. During food ingestion, masticatory muscles generate the ...required masticatory force. The magnitude of applied masticatory force has long been believed to be closely correlated with the shape of the jawbone. However, both the mechanism underlying this correlation and evidence of causation remain largely to be determined. Here, we established a novel mouse model of increased mastication in which mice were fed with a hard diet (HD) to elicit greater masticatory force. A novel in silico computer simulation indicated that the masticatory load onto the jawbone leads to the typical bone profile seen in the individuals with strong masticatory force, which was confirmed by in vivo micro-computed tomography (micro-CT) analyses. Mechanistically, increased mastication induced Insulin-like growth factor (IGF)-1 and suppressed sclerostin in osteocytes. IGF-1 enhanced osteoblastogenesis of the cells derived from tendon. Together, these findings indicate that the osteocytes balance the cytokine expression upon the mechanical loading of increased mastication, in order to enhance bone formation. This bone formation leads to morphological change in the jawbone, so that the bone adapts to the mechanical environment to which it is exposed.
For safe and sound utilization of the applications made of polylactic acid that output an electric signal to an intended mechanical input within an undesirable thermal environment, the transient ...thermoelectroelastic field is investigated for an infinite cylinder with D∞ symmetry subjected to shear stress as an intended mechanical input and temperature as an unfavorable thermal environment. By use of the analytical technique constructed previously, the field quantities are represented in terms of the elastic, piezoelastic, and thermoelastic displacement potential functions and the electric potential function, and the governing equations for these functions are presented. Then, the analytical solutions of the transient and non-axisymmetric field quantities are obtained using the Fourier and Laplace transformations with respect to the axial coordinate and time variable, respectively, and the Fourier expansion with respect to the circumferential coordinate. Subsequently, numerical calculations are performed to investigate the field due to the shear stress or temperature. As a result, the structures of respective fields are elucidated and the effect of thermal disturbance on the output signal to mechanical input is investigated quantitatively, both of which illustrate the significance of transient and three-dimensional analysis.
To improve the practicability of investigating devices composed of a body with D∞ symmetry, aiming at safe and sound operation, the electroelastic field was investigated for a strip with finite ...thickness subjected to a shear stress distribution that models a mechanical load input to such a device. An analytical technique constructed previously and the Fourier transformation technique with respect to the in-plane coordinates were employed. Then, the three-dimensional distributions of the electroelastic field quantities, such as displacement, electric potential, electric field, strain, stress, and electric displacement, were determined. Through the use of numerical calculations in which it is assumed that the device receives a mechanical load input and produces an electric signal output, the structure of the electroelastic field was investigated. It was found that the precise determination of electric displacement as an electric signal output required three-dimensional analysis considering the electroelastic coupling effect, whereas the stress-strain relation was substantially elastic. Then, it was found that the effect of finite thickness on the field needed to be considered for a relatively thin strip with a thickness comparable to, or less than, the effective width of the surface shear distribution. Moreover, from an application viewpoint, the results suggested that the optimal thickness to maximize an electric signal output exists.
Osteocytes are vital for regulating bone remodeling by sensing the flow-induced mechanical stimuli applied to their cell processes. In this mechanosensing mechanism, tethering elements (TEs) ...connecting the osteocyte process with the canalicular wall potentially amplify the strain on the osteocyte processes. The ultrastructure of the osteocyte processes and canaliculi can be visualized at a nanometer scale using high-resolution imaging via ultra-high voltage electron microscopy (UHVEM). Moreover, the irregular shapes of the osteocyte processes and the canaliculi, including the TEs in the canalicular space, should considerably influence the mechanical stimuli applied to the osteocytes. This study aims to characterize the roles of the ultrastructure of osteocyte processes and canaliculi in the mechanism of osteocyte mechanosensing. Thus, we constructed a high-resolution image-based model of an osteocyte process and a canaliculus using UHVEM tomography and investigated the distribution and magnitude of flow-induced local strain on the osteocyte process by performing fluid–structure interaction simulation. The analysis results reveal that local strain concentration in the osteocyte process was induced by a small number of TEs with high tension, which were inclined depending on the irregular shapes of osteocyte processes and canaliculi. Therefore, this study could provide meaningful insights into the effect of ultrastructure of osteocyte processes and canaliculi on the osteocyte mechanosensing mechanism.
Mammalian embryogenesis proceeds in utero with the support of nutrients and gases from maternal tissues. However, the contribution of the mechanical environment provided by the uterus to ...embryogenesis remains unaddressed. Notably, how intrauterine pressures are produced, accurately adjusted, and exerted on embryos are completely unknown. Here, we find that Reichert’s membrane, a specialized basement membrane that wraps around the implanted mouse embryo, plays a crucial role as a shock absorber to protect embryos from intrauterine pressures. Notably, intrauterine pressures are produced by uterine smooth muscle contractions, showing the highest and most frequent periodic peaks just after implantation. Mechanistically, such pressures are adjusted within the sealed space between the embryo and uterus created by Reichert’s membrane and are involved in egg-cylinder morphogenesis as an important biomechanical environment in utero. Thus, we propose the buffer space sealed by Reichert’s membrane cushions and disperses intrauterine pressures exerted on embryos for egg-cylinder morphogenesis.
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•Smooth muscle contractions exert high and periodic intrauterine pressures on embryos•Buffer space made by Reichert’s membrane protects embryos from intrauterine pressures•Intrauterine pressures are necessary to specify distal visceral endoderm correctly•Reduced pressures restore the deformed shape of Reichert’s-membrane-deficient embryos
Ueda et al. reveal that intrauterine pressures produced by uterine smooth muscle contractions show the highest and most frequent periodic peaks just after mouse embryo implantation. Reichert’s membrane, a specialized basement membrane that wraps around the implanted embryo, plays a crucial role as a shock absorber of intrauterine pressures.
During morphogenesis in development, multicellular tissues deform by mechanical forces induced by spatiotemporally regulated cellular activities, such as cell proliferation and constriction. Various ...morphologies are formed because of various spatiotemporal combinations and sequences of multicellular activities. Despite its potential to variations, morphogenesis is a surprisingly robust process, in which qualitatively similar morphologies are reproducibly formed even under spatiotemporal fluctuation of multicellular activities. To understand these essential characteristics of tissue morphogenesis, which involves the coexistence of various morphologies and robustness of the morphogenetic process, in this study, we propose a novel approach to capture the overall view of morphogenesis from mechanical viewpoints. This approach will enable visualization of the energy landscape, which includes morphogenetic processes induced by admissible histories of cellular activities. This approach was applied to investigate the morphogenesis of a sheet-like tissue with curvature, where it deformed to a concave or convex morphology depending on the history of growth and constriction. Qualitatively different morphologies were produced by bifurcation of the valley in the energy landscape. The depth and steepness of the valley near the stable states represented the degree of robustness to fluctuations of multicellular activities. Furthermore, as a realistic example, we showed an application of this approach to luminal folding observed in the initial stage of intestinal villus formation. This approach will be helpful to understand the mechanism of how various morphologies are formed and how tissues reproducibly achieve specific morphologies.
The cerebellum has a unique morphology characterized by fine folds called folia. During cerebellar morphogenesis, folia formation (foliation) proceeds with granule cell (GC) proliferation in an ...external granular layer, and subsequent cell migration to an internal granular layer (IGL). GC migration is guided along Bergmann glial (BG) fibers, whose orientation depends on the deformation of cerebellar tissue during folia formation. The aim of this study is to investigate the contribution of the fiber-guided GC migration on folia formation from a mechanical viewpoint. Based on a continuum mechanics model of cerebellar tissue deformation and GC dynamics, we simulated foliation process caused by GC proliferation and migration. By changing migration speeds, we showed that the fiber-guided GC migration caused the non-uniform accumulation of GCs and folia lengthening. Furthermore, the simulation of impaired GC migration under pathological conditions, where GCs did not migrate along BG fibers, revealed that fiber-guided GC migration was necessary for folia lengthening. These simulation results successfully recapitulated the features of physiological and pathological foliation processes and validated the mechanisms that guidance of GC migration by BG fibers causes folia lengthening accompanied by non-uniform IGL. Our computational approach will help us understand biological and physical morphogenesis mechanisms, facilitated by interactions between cellular activities and tissue behaviors.
Microstructures of cortical and cancellous bones are altered continually by load-adaptive remodeling; in addition, their cellular mechanisms are similar despite the remarkably different porosities. ...The cortico-cancellous transitional zone is a site of vigorous remodeling, and intracortical remodeling cavitates the inner cortex to promote its trabecularization, which is considered the main cause of bone loss because of aging. Therefore, to prevent and treat age-related cortical bone loss effectively, it is indispensable to gain an integrated understanding of the cortical to the cancellous bone transformation via remodeling. We propose a novel theoretical concept to account for the transformation of dense cortical bone to porous cancellous bone. We develop a mathematical model of cortical and cancellous bone remodeling based on the concept that bone porosity is determined by the balance between the load-bearing function of mineralized bone and the material-transporting function of bone marrow. Remodeling simulations using this mathematical model enable the reproduction of the microstructures of cortical and cancellous bones simultaneously. Furthermore, current remodeling simulations have the potential to replicate cortical-to-cancellous bone transformation based on changes in the local balance between bone formation and resorption. We anticipate that the proposed mathematical model of cortical and cancellous bone remodeling will contribute to highlighting the essential features of cortical bone loss due to trabecularization of the cortex and help predict its spatial and temporal behavior during aging.
•A novel theoretical concept to account for cortical-to-cancellous bone transformation is proposed.•A remodeling model to reproduce cortical and cancellous bone microstructures is developed.•The remodeling simulation replicates cortical-to-cancellous bone transformation.•The proposed method is valuable in clinical applications such as in predicting age-related cortical bone loss.
Trabecula, an anatomical unit of the cancellous bone, is a porous material that consists of a lamellar bone matrix and interstitial fluid in a lacuno-canalicular porosity. The flow of interstitial ...fluid caused by deformation of the bone matrix is believed to initiate a mechanical response in osteocytes for bone remodeling. In order to clarify the effect of the lamellar structure of the bone matrix—i.e., variations in material properties—on the fluid flow stimuli to osteocytes embedded in trabeculae, we investigated the mechanical behavior of an individual trabecula subjected to cyclic loading based on poroelasticity. We focused on variations in the trabecular permeability and developed an analytical solution containing both transient and steady-state responses for interstitial fluid pressure in a single trabecular model represented by a multilayered two-dimensional poroelastic slab. Based on the obtained solution, we calculated the pressure and seepage velocity of the interstitial fluid in lacuno-canalicular porosity, within the single trabecula, under various permeability distributions. Poroelastic analysis showed that a heterogeneous distribution of permeability produces remarkable variations in the fluid pressure and seepage velocity in the cross section of the individual trabecula, and suggests that fluid flow stimuli to osteocytes are mostly governed by the value of permeability in the neighborhood of the trabecular surfaces if there is no difference in the average permeability in a single trabecula.
It is well-established that cyclic, but not static, mechanical loading has anabolic effects on bone. However, the function describing the relationship between the loading frequency and the amount of ...bone adaptation remains unclear. Using a combined experimental and computational approach, this study aimed to investigate whether trabecular bone mechano-regulation is controlled by mechanical signals in the local
environment and dependent on loading frequency. Specifically, by combining
micro-computed tomography (micro-CT) imaging with micro-finite element (micro-FE) analysis, we monitored the changes in microstructural as well as the mechanical
environment strain energy density (SED) and SED gradient of mouse caudal vertebrae over 4 weeks of either cyclic loading at varying frequencies of 2, 5, or 10 Hz, respectively, or static loading. Higher values of SED and SED gradient on the local tissue level led to an increased probability of trabecular bone formation and a decreased probability of trabecular bone resorption. In all loading groups, the SED gradient was superior in the determination of local bone formation and resorption events as compared to SED. Cyclic loading induced positive net (re)modeling rates when compared to sham and static loading, mainly due to an increase in mineralizing surface and a decrease in eroded surface. Consequently, bone volume fraction increased over time in 2, 5, and 10 Hz (+15%, +21% and +24%,
≤ 0.0001), while static loading led to a decrease in bone volume fraction (-9%,
≤ 0.001). Furthermore, regression analysis revealed a logarithmic relationship between loading frequency and the net change in bone volume fraction over the 4 week observation period (
= 0.74). In conclusion, these results suggest that trabecular bone adaptation is regulated by mechanical signals in the local
environment and furthermore, that mechano-regulation is logarithmically dependent on loading frequency with frequencies below a certain threshold having catabolic effects, and those above anabolic effects. This study thereby provides valuable insights toward a better understanding of the mechanical signals influencing trabecular bone formation and resorption in the local
environment.
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