Modeling trabecular bone adaptation to local bending load regulated by mechanosensing osteocytes

Cancellous bone has a complicated three-dimensional porous microstructure that consists of strut-like or plate-like trabeculae. The arrangement of the trabeculae is remodeled throughout the organism’s lifetime to functionally adapt to the surrounding mechanical environment. During bone remodeling, osteocytes buried in the bone matrix are believed to play a pivotal role as mechanosensory cells and help regulate the coupling of osteoclastic bone resorption and osteoblastic bone formation according to the mechanical stimuli. Previously, we constructed a mathematical model of trabecular bone remodeling incorporating cellular mechanosensing and intercellular signal transmission, in which osteocytes are assumed to sense the flow of interstitial fluid as a mechanical stimulus that regulates bone remodeling. Our remodeling simulation could describe the reorientation of a single strut-like trabecula under uniaxial loading. In the present study, to investigate the effects of a bending load on trabecular bone remodeling, we simulated the morphological change in a single trabecula under a cyclic bending load based on our mathematical model. The simulation results showed that the application of the bending load influences not only the formation of the plate-like trabecula but also the changes in trabecular topology. These results suggest the possibility that the characteristic trabecular morphology, such as the strut-like or plate-like form, is determined depending on the local mechanical environment

Interstitial fluid flow in canaliculi as a mechanical stimulus for cancellous bone remodeling: in silico validation

Cancellous bone has a dynamic 3-dimensional architecture of trabeculae, the arrangement of which is continually reorganized via bone remodeling to adapt to the mechanical environment. Osteocytes are currently believed to be the major mechanosensory cells and to regulate osteoclastic bone resorption and osteoblastic bone formation in response to mechanical stimuli. We previously developed a mathematical model of trabecular bone remodeling incorporating the possible mechanisms of cellular mechanosensing and intercellular communication in which we assumed that interstitial fluid flow activates the osteocytes to regulate bone remodeling. While the proposed model has been validated by the simulation of remodeling of a single trabecula, it remains unclear whether it can successfully represent in silico the functional adaptation of cancellous bone with its multiple trabeculae. In the present study, we demonstrated the response of cancellous bone morphology to uniaxial or bending loads using a combination of our remodeling model with the voxel finite element method. In this simulation, cancellous bone with randomly arranged trabeculae remodeled to form a well-organized architecture oriented parallel to the direction of loading, in agreement with the previous simulation results and experimental findings. These results suggested that our mathematical model for trabecular bone remodeling enables us to predict the reorganization of cancellous bone architecture from cellular activities. Furthermore, our remodeling model can represent the phenomenological law of bone transformation toward a locally uniform state of stress or strain at the trabecular level

Theoretical concept of cortical to cancellous bone transformation

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

Development of continuum-based particle models of cell growth and proliferation for simulating tissue morphogenesis

Biological tissues acquire various characteristic shapes through morphogenesis. Tissue shapes result from the spatiotemporally heterogeneous cellular activities influenced by mechanical and biochemical environments. To investigate multicellular tissue morphogenesis, this study aimed to develop a novel multiscale method that can connect each cellular activity to the mechanical behaviors of the whole tissue by constructing continuum-based particle models of cellular activities. This study proposed mechanical models of cell growth and proliferation that are expressed as volume expansion and cell division by extending the material point method. By simulating cell hypertrophy and proliferation under both free and constraint conditions, the proposed models demonstrated potential for evaluating the mechanical state and tracing cells throughout tissue morphogenesis. Moreover, the effect of a cell size checkpoint was incorporated into the cell proliferation model to investigate the mechanical behaviors of the whole tissue depending on the condition of cellular activities. Consequently, the accumulation of strain energy density was suppressed because of the influence of the checkpoint. In addition, the whole tissues acquired different shapes depending on the influence of the checkpoint. Thus, the models constructed herein enabled us to investigate the change in the mechanical behaviors of the whole tissue according to each cellular activity depending on the mechanical state of the cells during morphogenesis

Crystallographic analysis of nano-structured bainitic steels

A 0.79C-1.5Si-1.98Mn-0.98Cr-0.24Mo-1.06Al-1.58Co (wt%) steel was isothermally heat treated at 200 and 350&deg;C bainitic transformation temperatures. The microstructure was consisted of bainitic ferrite lath and retained austenite for both heat treatment conditions. The crystallographic analysis revealed that the bainitic ferrite laths are close to the Nishiyama-Wassermann orientation relationship with their parent austenite. The isothermal bainite transformation temperature has a significant effect on the retained austenite characteristics and the variant selection of the bainitic ferrite laths. In general, a decrease in the isothennal bainite transformation temperature refined the bainitic structure and weakened the variant selection.<br /

An energy landscape approach to understanding variety and robustness in tissue morphogenesis

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

Prediction Of Lateral Vibration Behavior Of Integrally Geared Centrifugal Compressor During Synchronous Motor Startup By Transient Torsional-Lateral Coupled Analysis

LectureStartup transients of both torsional and lateral vibration behaviors of an integrally geared centrifugal compressor driven by a synchronous motor are examined by transient torsional-lateral coupled analyses, and the numerical calculation results are evaluated using the field measurements as a benchmark. Since linear bearing coefficients are employed in the numerical simulation instead of more sophisticated nonlinear bearing model, bilinear stiffness is additionally considered to reflect the effects of the rotor confinement within the bearing clearance. Moreover, temporary teeth separation of the gear meshing and engagement at the backside during torque reversal is also considered in the numerical calculation. The transient lateral vibration behavior of the pinion rotor during the synchronous motor’s startup is successfully replicated. Both (a) bilinear stiffness of the pinion rotor bearings due to rotor restraint within the bearing clearance, and (b) effect of temporary teeth separation within the backlash and engagement at the backside because of torque reversal, are found to strongly influence the numerical predictions

Pentose oxidation by acetic acid bacteria led to a finding of membrane-bound purine nucleosidase

D-Ribose and 2-deoxy-D-ribose were oxidized to 4- keto-D-ribonate and 2-deoxy-4-keto-D-ribonate respectively by oxidative fermentation, and the chemical structures of the oxidation products were confirmed to be as expected. Both pentoses are important sugar components of nucleic acids. When examined, purine nucleosidase activity predominated in the membrane fraction of acetic acid bacteria. This is perhaps the first finding of membrane-bound purine nucleosidase.Centro de Investigación y Desarrollo en Fermentaciones Industriale

Membrane-bound glycerol dehydrogenase catalyzes oxidation of D-pentonates to 4-keto-D-pentonates, D-fructose to 5-keto-D-fructose, and D-psicose to 5-keto-D-psicose

A novel oxidation of D-pentonates to 4-keto-D-pentonates was analyzed with Gluconobacter Thailandicus NBRC 3258. D-Pentonate 4-dehydrogenase activity in the membrane fraction was readily inactivated by EDTA and it was reactivated by the addition of PQQ and Ca2+. D-Pentonate 4-dehydrogenase was purified to two different subunits, 80 and 14 kDa. The absorption spectrum of the purified enzyme showed no typical absorbance over the visible regions. The enzyme oxidized D-pentonates to 4-keto-D-pentonates at the optimum pH of 4.0. In addition, the enzyme oxidized D-fructose to 5-keto-D-fructose, D-psicose to 5-keto-D-psicose, including the other polyols such as, glycerol, D-ribitol, D-arabitol, and D-sorbitol. Thus, D-pentonate 4-dehydrogenase was found to be identical with glycerol dehydrogenase (GLDH), a major polyol dehydrogenase in Gluconobacter species. The reaction versatility of quinoprotein GLDH was notified in this study.Facultad de Ciencias ExactasCentro de Investigación y Desarrollo en Fermentaciones Industriale

Intrauterine Pressures Adjusted by Reichert's Membrane Are Crucial for Early Mouse Morphogenesis

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