Department of Biosystems Science, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan.
Department of Micro Engineering, Graduate School of Engineering, Kyoto University, Kyoto, Japan.
Sci Adv. 2020 Mar 6;6(10):eaax0938. doi: 10.1126/sciadv.aax0938. eCollection 2020 Mar.
Bone structure and function are maintained by well-regulated bone metabolism and remodeling. Although the underlying molecular and cellular mechanisms are now being understood, physiological and pathological states of bone are still difficult to predict due to the complexity of intercellular signaling. We have now developed a novel in silico experimental platform, V-Bone, to integratively explore bone remodeling by linking complex microscopic molecular/cellular interactions to macroscopic tissue/organ adaptations. Mechano-biochemical couplings modeled in V-Bone relate bone adaptation to mechanical loading and reproduce metabolic bone diseases such as osteoporosis and osteopetrosis. V-Bone also enables in silico perturbation on a specific signaling molecule to observe bone metabolic dynamics over time. We also demonstrate that this platform provides a powerful way to predict in silico therapeutic effects of drugs against metabolic bone diseases. We anticipate that these in silico experiments will substantially accelerate research into bone metabolism and remodeling.
骨骼结构和功能由良好调节的骨代谢和重塑维持。尽管现在已经了解了潜在的分子和细胞机制，但由于细胞间信号传递的复杂性，骨骼的生理和病理状态仍然难以预测。我们现在开发了一种新的计算实验平台，V-Bone，通过将复杂的微观分子/细胞相互作用与宏观组织/器官适应联系起来，综合探索骨骼重塑。V-Bone 中模拟的力生化耦合关系将骨骼适应与机械加载联系起来，并再现骨质疏松症和石骨症等代谢性骨病。V-Bone 还可以对特定信号分子进行虚拟扰动，以观察随时间推移的骨代谢动力学。我们还证明，该平台为预测针对代谢性骨病的药物的虚拟治疗效果提供了一种强大的方法。我们预计这些计算实验将大大加速对骨骼代谢和重塑的研究。
