Institute for Frontier Life and Medical Sciences, Kyoto University

Development of a novel in silico experimental platform for bone remodeling

Yoshitaka Kameo1,2,3, Yuki Miya2, Mikihito Hayashi4, Tomoki Nakashima4, Taiji Adachi1,2,3

(1 Institute for Frontier Life and Medical Sciences, Kyoto University, 2 Graduate School of Engineering, Kyoto University, 3 Graduate School of Biostudies, Kyoto University, 4 Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University)

”In silico experiments of bone remodeling explore metabolic diseases and their drug treatment”
Science Advances (2020) DOI: 10.1126/sciadv.aax0938

Abstract

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.

In this study, we have 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. The proposed in silico model was qualitatively verified from mechanical and biochemical viewpoints by reproducing bone adaptation to mechanical loading and metabolic bone diseases such as osteoporosis and osteopetrosis. To more rigorously validate the in silico model, we also demonstrated in silico perturbation of a specific signaling molecule, a standard in vivo technique in life science, and quantitatively compared the results with those from corresponding in vivo experiments. In silico perturbation enables observation of the spatial and temporal dynamics of bone remodeling, which is difficult to achieve in vivo. Last, we applied the in silico model to predict the therapeutic effects of various drugs against osteoporosis and showed that in silico medication experiments provide a powerful way to assess the effects of drugs on bone cells and morphology in clinically relevant scenarios

In conjunction with in vivo and in vitro experiments, in silico experiments provide a third avenue to explore bone metabolism. We anticipate that V-Bone will accelerate bone metabolism and remodeling studies through comprehensive understanding of molecular, cellular, tissue, and organ dynamics.

Schematic view of this study  (c)2020 aichan