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软骨生物分子调节过程中合成代谢与分解代谢动力学的细胞-基质模型

A cell-matrix model of anabolic and catabolic dynamics during cartilage biomolecule regulation.

作者信息

Saha Asit K, Kohles Sean S

机构信息

Center for Allaying Health Disparities through Research and Education (CADRE), Department of Mathematics and Computer Science, Central State University, Wilberforce, Ohio, 45384, USA.

出版信息

Int J Comput Healthc. 2012 Jan 1;1(3):214-228. doi: 10.1504/IJCIH.2012.046995.

Abstract

Physiologic regulation of extracellular matrix (ECM) in articular cartilage tissue is controlled by cellular and molecular mechanisms which are not fully understood. It has been observed that the synthesis of the ECM structural molecules, glycosaminoglycan and collagen are promoted by growth factors such as IGF-1 and TGF-β. Concomitant ECM degradation is promoted by a variety of cytokines such as IL-1. The clinical need for reparative therapies of articular cartilage is linked with its poor intrinsic healing capacity. The following modelling approach was applied to engineered cartilage as a platform for exploring cartilage biology and to introduce a predictive tool as a bioinformatic support system supporting regenerative therapies. Systems biology was adapted through a mathematical framework producing a computational intelligence paradigm to explore a controlled phasic regulatory influence of the inhibition and production of ECM biomolecules. Model outcomes describe a steady synthesis of ECM as a dependence on a cyclic influence of the catabolic action of proteases and anabolic action of growth factors. This relationship is shown quantitatively in a governing harmonic equation representing the simplified biological mechanisms of biomolecule homeostasis.

摘要

关节软骨组织中细胞外基质(ECM)的生理调节受细胞和分子机制控制,而这些机制尚未完全明确。据观察,诸如IGF - 1和TGF - β等生长因子可促进ECM结构分子、糖胺聚糖和胶原蛋白的合成。而诸如IL - 1等多种细胞因子则会促进ECM的降解。关节软骨修复治疗的临床需求与其自身较差的愈合能力相关。以下建模方法应用于工程化软骨,作为探索软骨生物学的平台,并引入一种预测工具作为支持再生治疗的生物信息学支持系统。系统生物学通过一个数学框架进行调整,产生一种计算智能范式,以探索ECM生物分子抑制和产生的受控阶段性调节影响。模型结果表明,ECM的稳定合成依赖于蛋白酶分解作用和生长因子合成作用的周期性影响。这种关系在一个表示生物分子稳态简化生物学机制的主导谐波方程中得到了定量体现。

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