Biomimetics Laboratory, Instituto de Biotecnología, Universidad Nacional de Colombia, Bogotá, Ciudad Universitaria, Colombia; Numerical Methods and Modeling Research Group (GNUM), Universidad Nacional de Colombia, Bogotá, Ciudad Universitaria, Colombia.
Department of Biology, Northeastern University, Boston, MA 02115, USA.
J Theor Biol. 2018 Oct 7;454:345-356. doi: 10.1016/j.jtbi.2018.04.015. Epub 2018 Apr 10.
Joints connect the skeletal components and enable movement. The appearance and development of articulations is due to different genetic, biochemical, and mechanical factors. In the embryonic stage, controlled biochemical processes are critical for organized growth. We developed a computational model, which predicts the appearance, location, and development of joints in the embryonic stage. Biochemical events are modeled with reaction diffusion equations with generic molecules representing molecules that 1) determine the site where the articulation will appear, 2) promote proliferation, and matrix synthesis, and 3) define articular cartilage. Our model accounts for cell differentiation from mesenchymal cells to pre-cartilaginous cells, then cartilaginous cells, and lastly articular cartilage. These reaction-diffusion equations were solved using the finite elements method. From a mesenchymal 'bud' of a phalanx, the model predicts growth, joint cleavage, joint morphology, and articular cartilage formation. Our prediction of the gene expression during development agrees with molecular expression profiles of joint development reported in literature. Our computational model suggests that initial rudiment dimensions affect diffusion profiles result in Turing patterns that dictate sites of cleavage thereby determining the number of joints in a rudiment.
关节连接骨骼成分并实现运动。关节的出现和发育归因于不同的遗传、生化和机械因素。在胚胎阶段,受控制的生化过程对于有序生长至关重要。我们开发了一种计算模型,用于预测胚胎阶段关节的出现、位置和发育。生化事件通过反应扩散方程建模,通用分子代表 1)确定关节出现位置的分子,2)促进增殖和基质合成的分子,以及 3)定义关节软骨的分子。我们的模型考虑了细胞从间充质细胞分化为软骨前细胞,然后再分化为软骨细胞,最后是关节软骨。这些反应扩散方程使用有限元方法求解。从指骨的间充质“芽”中,模型预测了生长、关节分裂、关节形态和关节软骨形成。我们对发育过程中基因表达的预测与文献中报道的关节发育的分子表达谱一致。我们的计算模型表明,初始芽体尺寸会影响扩散模式,从而产生决定分裂部位的图灵模式,从而确定芽体中的关节数量。