Studying the mechanical properties of the mandible and injury prediction under the effect of ossification factors.

BACKGROUND AND OBJECTIVE: It is essential to know the quantitative interactions between biological tissues and external mechanical and chemical stimuli. This assists the physicians to better know the quantitative behavior of the tissue and plan more effective therapy. In the literature, the effect of the chemical and mechanical loading was investigated on the bone biological cell activities and some mechanical features, but a lack of prediction of bone injury under the chemical and mechanical factors was sensed. Therefore, the present study aims to investigate the effects of the application of major chemical factors involved in ossification, including RANKL1 (Receptor Activator of Nuclear Factor Kappa Beta Ligand), PTH2 (Parathyroid Hormone), and OPG3 (Osteoprotegerin) on the mandibular bone biological osteoblast and osteoclast activities and mechanical properties. Moreover, the study assesses the bone injury possibility under uniform mastication pressure applied on the premolar tooth in terms of the mechanostat theory undergoing the effects of the chemical factors. METHODS: A 3D geometry of the mandible-tooth assembly was generated from the CT image dataset. The geometry was next purified, solidified, and exported to FEM4 (Finite Element Method) software to be meshed, where boundary conditions and loading were applied. Moreover, the mathematical system of differential equations to model the chemical factor effects on osteoblast and osteoclast activities as well as bone matrix volume fraction and elastic stiffness relations were applied. Next, the values of the equivalent strain were calculated to predict the injury states of the bone. RESULTS: The results complied with the literature data. The results showed that RANKL and PTH increased the values of the equivalent strain from 450 µÎµ to 11500 µÎµ, while OPG reduced that from 450 µÎµ to 300 µÎµ. CONCLUSIONS: Therefore, RANKL and PTH doses of this study put the bone at risk of injury compared to the baseline of no dose applied, while OPG secured the bone from injury.

Ca2+-dependent calcineurin/NFAT signaling in ß-adrenergic-induced cardiac hypertrophy.

Ca2+ is an important mediator in the ß-adrenergic-induced cardiac hypertrophy. The ß-adrenergic stimulation alters the Ca2+ transient characteristics including its oscillation frequency, diastolic and systolic levels which lead to the CaN activation and subsequent NFAT-dependent hypertrophic genes transcription. Moreover, ß-adrenergic-induced alterations in PKA and GSK3ß kinase activities in both the cytosol and the nucleus regulate NFAT nuclear translocation and contribute in its hypertrophic response. Due to the complex nature of CaN/NFAT signaling in cardiac cells, we use a computational approach to investigate the ß-adrenergic-induced CaN/NFAT activation in the cardiac myocytes. The presented model predicts well the main physiological characteristics of CaN/NFAT signaling in accordance with the experimental observations. The presented model establishes the previous experimental and mathematical results on the principal role of Ca2+ oscillation frequency in the CaN/NFAT signaling and shows that increase in Ca2+ oscillation frequency enhances CaN activity and its sensitivity to low ISO concentrations. The model illustrates that in addition to the known ISO effect on Ca2+ transient amplitude, ISO-induced alterations in Ca2+ oscillation frequency, PKA and GSK3ß kinase activities also greatly affect the ß-adrenergic-induced NFAT activity. We also found that PKA has both pro-hypertrophic and anti-hypertrophic effects on NFAT activation and is the main kinase in ISO-induced NFAT activation.

Investigating ß-adrenergic-induced cardiac hypertrophy through computational approach: classical and non-classical pathways.

The chronic stimulation of ß-adrenergic receptors plays a crucial role in cardiac hypertrophy and its progression to heart failure. In ß-adrenergic signaling, in addition to the well-established classical pathway, Gs/AC/cAMP/PKA, activation of non-classical pathways such as Gi/PI3K/Akt/GSK3ß and Gi/Ras/Raf/MEK/ERK contribute in cardiac hypertrophy. The signaling network of ß-adrenergic-induced hypertrophy is very complex and not fully understood. So, we use a computational approach to investigate the dynamic response and contribution of ß-adrenergic mediators in cardiac hypertrophy. The proposed computational model provides insights into the effects of ß-adrenergic classical and non-classical pathways on the activity of hypertrophic transcription factors CREB and GATA4. The results illustrate that the model captures the dynamics of the main signaling mediators and reproduces the experimental observations well. The results also show that despite the low portion of ß2 receptors out of total cardiac ß-adrenergic receptors, their contribution in the activation of hypertrophic mediators and regulation of ß-adrenergic-induced hypertrophy is noticeable and variations in ß1/ß2 receptors ratio greatly affect the ISO-induced hypertrophic response. The model results illustrate that GSK3ß deactivation after ß-adrenergic receptor stimulation has a major influence on CREB and GATA4 activation and consequent cardiac hypertrophy. Also, it is found through sensitivity analysis that PKB (Akt) activation has both pro-hypertrophic and anti-hypertrophic effects in ß-adrenergic signaling.

Application of Hyperelastic-based Active Mesh Model in Cardiac Motion Recovery.

Considering the nonlinear hyperelastic or viscoelastic nature of soft tissues has an important effect on modeling results. In medical applications, accounting nonlinearity begets an ill posed problem, due to absence of external force. Myocardium can be considered as a hyperelastic material, and variational approaches are proposed to estimate stiffness matrix, which take into account the linear and nonlinear properties of myocardium. By displacement estimation of some points in the four-dimensional cardiac magnetic resonance imaging series, using a similarity criterion, the elementary deformations are estimated, then using the Moore-Penrose inverse matrix approach, all point deformations are obtained. Using this process, the cardiac wall motion is quantized to mechanically determine local parameters to investigate the cardiac wall functionality. This process was implemented and tested over 10 healthy and 20 patients with myocardial infarction. In all patients, the process was able to precisely determine the affected region. The proposed approach was also compared with linear one and the results demonstrated its superiority respect to the linear model.