In silico experiments of bone remodeling explore metabolic diseases and their drug treatment

Sci Adv. 2020 Mar 6;6(10):eaax0938. doi: 10.1126/sciadv.aax0938. eCollection 2020 Mar.

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. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Remodeling / drug effects*
  • Computer Simulation*
  • Humans
  • Models, Biological*
  • Osteopetrosis* / drug therapy
  • Osteopetrosis* / metabolism
  • Osteopetrosis* / pathology
  • Osteoporosis* / drug therapy
  • Osteoporosis* / metabolism
  • Osteoporosis* / pathology