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Research of Quantitative Relation between Bone Remodeling Threshold and Several Cellular Pathways

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Tutor: GuoTongTong
School: Harbin Institute of Technology
Course: Mechanics
Keywords: cellular pathway,cytokine,bone remodeling threshold,quantitativerelationship
CLC: Q441
Type: Master's thesis
Year:  2013
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Abstract:
Many efforts have been put to show that cell signal pathways play animportant role in regulating the function of osteocyte, bone mass and boneremodeling. The process of bone metabolism is a result of internal cellularpathways and mechanics environment, which express as the change of boneremodeling threshold in the bone remodeling theory and lead to the change ofbone mineral density. Therefore, there is a certain quantitative relationshipbetween cellular pathways and bone remodeling threshold. This project is basedon bone remodeling equation in biomechanics research perspective. The purposeof the paper is to obtain the quantitative relationship between bone remodelingthreshold value and cellular pathways, so as to make the numerical simulationanalysis.For bone metabolism related cellular pathways, the mechanism of theseseveral cellular pathways has been summarized. Based on that, the representativecell cytokine is chosen from several cellular pathways. Then the quantitativerelationship between bone remodeling threshold k and several cellular pathwaysis fitted.With bone remodeling theory, a series of bone remodeling thresholds arecalculated, which based on the bone mineral density changes in the normalcontrol group and the genetic changes group of some literatures. Then combiningwith important cytokines experimental data of cellular pathways measured formnormal cell culture, the normal control group data regression analysis model isestablished. Finally the quantitative relationship is simulated and validated. Theexisting finite element model in the laboratory has been used as the initial valuefor simulating bone density changes in the gene change group. New simulationresults of pathway factors and bone remodeling thresholds are obtained.The simulation divided into two groups. We directly simulate BMD changeof literatures as the former simulation. The relative error of bone mineral densitysimulation is about0.8%. The maximum relative error of bone remodelingthreshold is20.77%and others are mostly about3%. Then the literature the bonemineral density corresponds to the model, which obtain the unity normalized databased on not change the rate of bone mineral density. We put0.7115as the initial value to continue the latter simulation. By comparing simulation results, therelative error of bone mineral density simulation is about0.2%. The maximumrelative error of bone remodeling threshold is12.97%and others are1%to2%.The latter simulation results are better than the previous. By comparing cytokinesof genetic change group in the simulation results with normal control group,which are consistent with the target cytokine genes changed in literatures. It alsoproved that the cellular pathways can¡¯t change independently and crossconduction between cellular pathways. The results of the bone remodelingthresholds are obtained by simulating the genetic change group, and we comparethem with theoretical calculation results. The comparison results show that it isrational about the multiple linear regression equation.The paper conclusion is that the quantitative relationship between severalcellular pathways and bone remodeling thresholds is established. The simulationalso proves that the fitted multiple linear regression equation is reasonable. Andthe process provides a new idea for clarifying the mechanism of bone remodelingby investigating the biomechanically signal transduction mechanism of bonemetabolism.
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