Computational modeling reveals a key role for polarized myeloid cells in controlling osteoclast activity during bone injury repair.
Computational modeling reveals a key role for polarized myeloid cells in controlling osteoclast activity during bone injury repair.
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DOI：
10.1038/s41598-021-84888-1
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发表时间：
2021-03-15
影响因子：
4.6
通讯作者：
Lynch CC
中科院分区：
文献类型：
--
作者：
Lo CH;Baratchart E;Basanta D;Lynch CC
成骨细胞和骨吸收破骨细胞控制骨损伤修复，并且已知骨髓源性细胞（例如单核细胞和巨噬细胞）会影响它们的行为。然而，使用生物学方法很难剖析这些多种细胞类型如何在骨髓内随着时间的推移相互协调和调节以恢复骨骼。相反，数学建模非常适合应对这一挑战。因此，我们生成了一个常微分方程（ODE）模型，该模型由从胫骨内损伤小鼠获得的实验数据（成骨细胞、破骨细胞、骨体积、促炎和抗炎骨髓细胞）提供支持。仅使用成骨细胞/破骨细胞群体的初始 ODE 结果表明，损伤后骨稳态无法恢复，但在整合促炎和抗炎骨髓细胞群体动态后，这个问题得到了解决。令人惊讶的是，ODE 显示总骨矿化/吸收峰值与成骨细胞/破骨细胞数量之间存在时间上的脱节。具体而言，该模型表明，破骨细胞活性必须发生很大变化（> 17 倍）才能使损伤后骨体积恢复到基线，并表明单独的成骨细胞/破骨细胞数量不足以预测骨修复的轨迹。重要的是，破骨细胞活性的值落在之前发布的值之内。这些数据强调了数学建模方法对于理解和揭示复杂生物过程新见解的价值。
Bone-forming osteoblasts and -resorbing osteoclasts control bone injury repair, and myeloid-derived cells such as monocytes and macrophages are known to influence their behavior. However, precisely how these multiple cell types coordinate and regulate each other over time within the bone marrow to restore bone is difficult to dissect using biological approaches. Conversely, mathematical modeling lends itself well to this challenge. Therefore, we generated an ordinary differential equation (ODE) model powered by experimental data (osteoblast, osteoclast, bone volume, pro- and anti-inflammatory myeloid cells) obtained from intra-tibially injured mice. Initial ODE results using only osteoblast/osteoclast populations demonstrated that bone homeostasis could not be recovered after injury, but this issue was resolved upon integration of pro- and anti-inflammatory myeloid population dynamics. Surprisingly, the ODE revealed temporal disconnects between the peak of total bone mineralization/resorption, and osteoblast/osteoclast numbers. Specifically, the model indicated that osteoclast activity must vary greatly (> 17-fold) to return the bone volume to baseline after injury and suggest that osteoblast/osteoclast number alone is insufficient to predict bone the trajectory of bone repair. Importantly, the values of osteoclast activity fall within those published previously. These data underscore the value of mathematical modeling approaches to understand and reveal new insights into complex biological processes.
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影响因子：
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