Calvo-Gallego José Luis, Manchado-Morales Pablo, Pivonka Peter, Martínez-Reina Javier
Departamento de Ingeniería Mecánica y Fabricación, Universidad de Sevilla, Seville, Spain.
School of Mechanical, Medical and Process Engineering, Queensland University of Technology, Brisbane, QLD, Australia.
Front Bioeng Biotechnol. 2023 Mar 7;11:1060158. doi: 10.3389/fbioe.2023.1060158. eCollection 2023.
Here we developed a spatio-temporal bone remodeling model to simulate the action of Basic Multicelluar Units (BMUs). This model is based on two major extensions of a temporal-only bone cell population model (BCPM). First, the differentiation into mature resorbing osteoclasts and mature forming osteoblasts from their respective precursor cells was modelled as an intermittent process based on precursor cells availability. Second, the interaction between neighbouring BMUs was considered based on a "metabolic cost" argument which warrants that no new BMU will be activated in the neighbourhood of an existing BMU. With the proposed model we have simulated the phases of the remodelling process obtaining average periods similar to those found in the literature: resorption ( days)-reversal (∼8 days)-formation (∼65 days)-quiescence (560-600 days) and an average BMU activation frequency of ∼1.6 BMUs/year/mm. We further show here that the resorption and formation phases of the BMU become coordinated only by the presence of TGF-β (transforming growth factor ), i.e., a major coupling factor stored in the bone matrix. TGF-β is released through resorption so upregulating osteoclast apoptosis and accumulation of osteoblast precursors, i.e., facilitating the transition from the resorption to the formation phase at a given remodelling site. Finally, we demonstrate that this model can explain targeted bone remodelling as the BMUs are steered towards damaged bone areas in order to commence bone matrix repair.
在此，我们开发了一种时空骨重塑模型，以模拟基本多细胞单位（BMU）的作用。该模型基于仅含时间变量的骨细胞群体模型（BCPM）的两个主要扩展。首先，从各自的前体细胞分化为成熟的吸收性破骨细胞和成熟的形成性成骨细胞被建模为一个基于前体细胞可用性的间歇性过程。其次，基于“代谢成本”的观点考虑了相邻BMU之间的相互作用，这确保在现有BMU的邻域内不会激活新的BMU。利用所提出的模型，我们模拟了重塑过程的各个阶段，获得了与文献中发现的平均周期相似的结果：吸收（约 天）-逆转（约8天）-形成（约65天）-静止（560 - 600天），以及平均BMU激活频率约为1.6个BMU/年/毫米。我们在此进一步表明，BMU的吸收和形成阶段仅通过转化生长因子β（TGF-β）的存在而变得协调，TGF-β是一种储存在骨基质中的主要耦合因子。TGF-β通过吸收释放，从而上调破骨细胞凋亡和成骨细胞前体的积累，即在给定的重塑部位促进从吸收阶段向形成阶段的转变。最后，我们证明该模型可以解释靶向性骨重塑，因为BMU被导向受损骨区域以开始骨基质修复。
