软骨生物分子调节过程中合成代谢和分解代谢动力学的细胞基质模型。

Asit K Saha, Sean S Kohles
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引用次数: 18

摘要

关节软骨组织细胞外基质(ECM)的生理调控是由细胞和分子机制控制的,但目前尚不完全清楚。研究发现,生长因子如IGF-1和TGF-β促进了ECM结构分子、糖胺聚糖和胶原蛋白的合成。伴随的ECM降解由多种细胞因子如IL-1促进。临床对关节软骨修复治疗的需求与关节软骨较差的内在愈合能力有关。以下建模方法应用于工程软骨,作为探索软骨生物学的平台,并引入预测工具作为支持再生治疗的生物信息学支持系统。系统生物学通过产生计算智能范式的数学框架进行了调整,以探索ECM生物分子的抑制和产生的受控相位调节影响。模型结果描述了ECM的稳定合成依赖于蛋白酶的分解代谢作用和生长因子的合成代谢作用的循环影响。这种关系在代表生物分子稳态的简化生物学机制的控制调和方程中定量地显示出来。
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A cell-matrix model of anabolic and catabolic dynamics during cartilage biomolecule regulation.

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.

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