Investigation of Osteoclast Resorption Mechanisms in a Hybrid Cellular Automaton Model of Bone Remodeling

2007 ◽  
Author(s):  
Charles L. Penninger ◽  
Ryan K. Roeder ◽  
Glen L. Niebur ◽  
John E. Renaud
Keyword(s):  
Cellular Automaton ◽  
Bone Remodeling ◽  
Mechanical Loading ◽  
Living Tissue ◽  
Basic Multicellular Unit ◽  
Mechanical Loads ◽  
Continuous Formation ◽  
Damage Repair ◽  
Biological Environment ◽  
Osteoclast Resorption

Bone is a living tissue which is continually adapting to its biological environment via continuous formation and resorption. It is generally accepted that bone remodeling occurs in response to daily mechanical loading. The remodeling process enables various functions, such as damage repair, adaptation to mechanical loads, and mineral homeostasis [1]. The cells that are responsible for the bone remodeling process are the bone resorbing osteoclasts and the bone forming osteoblasts. These cells closely coordinate their actions in a basic multicellular unit to renew “packets” of bone.

Analysis and design of thermo-mechanical interfaces

2012 ◽  
Vol 60 (2) ◽  
pp. 205-213
Author(s):  
K. Dems ◽  
Z. Mróz
Keyword(s):  
Optimality Conditions ◽  
Mechanical Loading ◽  
Material Properties ◽  
Structural Response ◽  
External Boundary ◽  
Mechanical Loads ◽  
Internal Interface ◽  
Analysis And Design ◽  
First Order ◽  
Mechanical Nature

Abstract. An elastic structure subjected to thermal and mechanical loading with prescribed external boundary and varying internal interface is considered. The different thermal and mechanical nature of this interface is discussed, since the interface form and its properties affect strongly the structural response. The first-order sensitivities of an arbitrary thermal and mechanical behavioral functional with respect to shape and material properties of the interface are derived using the direct or adjoint approaches. Next the relevant optimality conditions are formulated. Some examples illustrate the applicability of proposed approach to control the structural response due to applied thermal and mechanical loads.

scholarly journals Osteoblast and Osteoclast Activity Affect Bone Remodeling Upon Regulation by Mechanical Loading-Induced Leukemia Inhibitory Factor Expression in Osteocytes

2020 ◽  
Vol 7 ◽  
Author(s):  
Jingke Du ◽  
Jiancheng Yang ◽  
Zihao He ◽  
Junqi Cui ◽  
Yiqi Yang ◽  
...  
Keyword(s):  
Bone Remodeling ◽  
Mechanical Loading ◽  
Leukemia Inhibitory Factor ◽  
Fluid Shear Stress ◽  
Bone Structure ◽  
Inhibitory Factor ◽  
Tartrate Resistant Acid Phosphatase ◽  
Osteoclast Activity ◽  
Microgravity Simulation

PurposeBone remodeling is affected by mechanical stimulation. Osteocytes are the primary mechanical load-sensing cells in the bone, and can regulate osteoblast and osteoclast activity, thus playing a key role in bone remodeling. Further, bone mass during exercise is also regulated by Leukemia inhibitory factor (LIF). This study aimed to investigate the role of LIF in the mechanical response of the bone, in vivo and in vitro, and to elucidate the mechanism by which osteocytes secrete LIF to regulate osteoblasts and osteoclasts.MethodsA tail-suspension (TS) mouse model was used in this study to mimic muscular disuse. ELISA and immunohistochemistry were performed to detect bone and serum LIF levels. Micro-computed tomography (CT) of the mouse femurs was performed to measure three-dimensional bone structure parameters. Fluid shear stress (FSS) and microgravity simulation experiments were performed to study mechanical stress-induced LIF secretion and its resultant effects. Bone marrow macrophages (BMMs) and bone mesenchymal stem cells (BMSCs) were cultured to induce in vitro osteoclastogenesis and osteogenesis, respectively.ResultsMicro-CT results showed that TS mice exhibited deteriorated bone microstructure and lower serum LIF expression. LIF secretion by osteocytes was promoted by FSS and was repressed in a microgravity environment. Further experiments showed that LIF could elevate the tartrate-resistant acid phosphatase activity in BMM-derived osteoclasts through the STAT3 signaling pathway. LIF also enhanced alkaline phosphatase staining and osteogenesis-related gene expression during the osteogenic differentiation of BMSCs.ConclusionMechanical loading affected LIF expression levels in osteocytes, thereby altering the balance between osteoclastogenesis and osteogenesis.

High Fidelity Computational Model of Bone Remodeling Cellular Mechanisms

2010 ◽  
Author(s):  
Charles L. Penninger ◽  
Andrés Tovar ◽  
Glen L. Niebur ◽  
John E. Renaud
Keyword(s):  
Bone Remodeling ◽  
Computational Models ◽  
Bone Adaptation ◽  
Daily Activities ◽  
High Fidelity ◽  
Mechanical Stimuli ◽  
Cellular Activity ◽  
Cellular Mechanisms ◽  
Mechanical Loads ◽  
Metabolic Activities

One of the most intriguing aspects of bone is its ability to grow, repair damage, adapt to mechanical loads, and maintain mineral homeostasis [1]. It is generally accepted that bone adaptation occurs in response to the mechanical demands of our daily activities; moreover, strain and microdamage have been implicated as potential stimuli that regulate bone remodeling [2]. Computational models have been used to simulate remodeling in an attempt to better understand the metabolic activities which possess the key information of how this process is carried out [3]. At present, the connection between the cellular activity of remodeling and the applied mechanical stimuli is not fully understood. Only a few mathematical models have been formulated to characterize the remolding process in terms of the cellular mechanisms that occur [4,5].

An Analysis of the Cooperative Mechano-Sensitive Feedback Between Intracellular Signaling, Focal Adhesion Development, and Stress Fiber Contractility

2011 ◽  
Vol 78 (4) ◽  
Author(s):  
Amit Pathak ◽  
Robert M. McMeeking ◽  
Anthony G. Evans ◽  
Vikram S. Deshpande
Keyword(s):  
Mechanical Loading ◽  
Focal Adhesion ◽  
Intracellular Signaling ◽  
Feedback Loop ◽  
Adhesion Formation ◽  
Focal Adhesions ◽  
Stress Fiber ◽  
Mechanical Loads ◽  
Signaling Model ◽  
Wide Range

Cells communicate with their external environment via focal adhesions and generate activation signals that in turn trigger the activity of the intracellular contractile machinery. These signals can be triggered by mechanical loading that gives rise to a cooperative feedback loop among signaling, focal adhesion formation, and cytoskeletal contractility, which in turn equilibrates with the applied mechanical loads. We devise a signaling model that couples stress fiber contractility and mechano-sensitive focal adhesion models to complete this above mentioned feedback loop. The signaling model is based on a biochemical pathway where IP3 molecules are generated when focal adhesions grow. These IP3 molecules diffuse through the cytosol leading to the opening of ion channels that disgorge Ca2+ from the endoplasmic reticulum leading to the activation of the actin/myosin contractile machinery. A simple numerical example is presented where a one-dimensional cell adhered to a rigid substrate is pulled at one end, and the evolution of the stress fiber activation signal, stress fiber concentrations, and focal adhesion distributions are investigated. We demonstrate that while it is sufficient to approximate the activation signal as spatially uniform due to the rapid diffusion of the IP3 through the cytosol, the level of the activation signal is sensitive to the rate of application of the mechanical loads. This suggests that ad hoc signaling models may not be able to capture the mechanical response of cells to a wide range of mechanical loading events.

Simulation of Bone Mechanical Adaptation Using Different Mathematical Models: A Comparative Numerical Study

2015 ◽  
Vol 638 ◽  
pp. 183-188
Author(s):  
Emil Nuțu ◽  
Horia Miron Gheorghiu
Keyword(s):  
Mathematical Models ◽  
Bone Remodeling ◽  
Numerical Study ◽  
Original Strain ◽  
Mechanical Loads ◽  
Mechanical Adaptation ◽  
Density Distributions ◽  
The University ◽  
University Of Manchester ◽  
Density Equation

The adaptation of bones to mechanical loads or bone remodeling can be simulated using specific mathematical models in conjunction with the finite element method. There are several theories proposed within the literature for the prediction of the bone behavior under mechanical loads and all have been used successfully, within certain limits of prediction details, but no unanimous acceptance have been reported yet. Within this context, it is important to know the differences and similarities between the results which these theories can produce, in order to improve their interpretation. On the basics of the above observation, the paper presents the comparison between density distributions achieved using three different models of bone remodeling: the original strain energy density equation developed at the University of Nijmegen, the principle of cellular accommodation incorporated into the Nijmegen model and the variant developed at the University of Manchester obtained by adding the quadric term which eliminates the density accumulation at physiologically unrealistic high loads. It is shown, using a suggestive test problem, that the three models generate significantly different results.

scholarly journals The Role of the Loading Condition in Predictions of Bone Adaptation in a Mouse Tibial Loading Model

2021 ◽  
Vol 9 ◽  
Author(s):  
Vee San Cheong ◽  
Visakan Kadirkamanathan ◽  
Enrico Dall’Ara
Keyword(s):  
Bone Remodeling ◽  
Mechanical Loading ◽  
Axial Load ◽  
Bone Adaptation ◽  
Combined Loading ◽  
Micro Ct ◽  
Loading Conditions ◽  
Physiological Loading ◽  
Physiological Load ◽  
Significant Difference

The in vivo mouse tibial loading model is used to evaluate the effectiveness of mechanical loading treatment against skeletal diseases. Although studies have correlated bone adaptation with the induced mechanical stimulus, predictions of bone remodeling remained poor, and the interaction between external and physiological loading in engendering bone changes have not been determined. The aim of this study was to determine the effect of passive mechanical loading on the strain distribution in the mouse tibia and its predictions of bone adaptation. Longitudinal micro-computed tomography (micro-CT) imaging was performed over 2 weeks of cyclic loading from weeks 18 to 22 of age, to quantify the shape change, remodeling, and changes in densitometric properties. Micro-CT based finite element analysis coupled with an optimization algorithm for bone remodeling was used to predict bone adaptation under physiological loads, nominal 12N axial load and combined nominal 12N axial load superimposed to the physiological load. The results showed that despite large differences in the strain energy density magnitudes and distributions across the tibial length, the overall accuracy of the model and the spatial match were similar for all evaluated loading conditions. Predictions of densitometric properties were most similar to the experimental data for combined loading, followed closely by physiological loading conditions, despite no significant difference between these two predicted groups. However, all predicted densitometric properties were significantly different for the 12N and the combined loading conditions. The results suggest that computational modeling of bone’s adaptive response to passive mechanical loading should include the contribution of daily physiological load.

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