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Mechanical Stimuli in the Local In Vivo Environment in Bone: Computational Approaches Linking Organ-Scale Loads to Cellular Signals

  • Biomechanics (G Niebur and J Wallace, Section Editors)
  • Published:
Current Osteoporosis Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Connecting organ-scale loads to cellular signals in their local in vivo environment is a current challenge in the field of bone (re)modelling. Understanding this critical missing link would greatly improve our ability to anticipate mechanotransduction during different modes of stimuli and the resultant cellular responses. This review characterises computational approaches that could enable coupling links across the multiple scales of bone.

Recent Findings

Current approaches using strain and fluid shear stress concepts have begun to link organ-scale loads to cellular signals; however, these approaches fail to capture localised micro-structural heterogeneities. Furthermore, models that incorporate downstream communication from osteocytes to osteoclasts, bone-lining cells and osteoblasts, will help improve the understanding of (re)modelling activities. Incorporating this potentially key information in the local in vivo environment will aid in developing multiscale models of mechanotransduction that can predict or help describe resultant biological events related to bone (re)modelling.

Summary

Progress towards multiscale determination of the cell mechanical environment from organ-scale loads remains elusive. Construction of organ-, tissue- and cell-scale computational models that include localised environmental variation, strain amplification and intercellular communication mechanisms will ultimately help couple the hierarchal levels of bone.

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Funding

This work has been supported by the European Union (ERC Advanced MechAGE, ERC-2016-ADG-741883; Marie-Curie-COFUND CaP+MECHLOAD, WHRI-ACADEMY-608765).

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  1. Institute for Biomechanics, ETH Zurich, Leopold-Ruzicka-Weg 4, 8093, Zürich, Switzerland

    Graeme R. Paul, Angad Malhotra & Ralph Müller

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  1. Graeme R. Paul
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Correspondence to Ralph Müller.

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Ralph Müller reports receiving personal fees from Amgen.

Graeme Paul and Angad Malhotra declare no conflict of interest.

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This review article does not contain unpublished data from human or animal studies performed by any of the authors.

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Paul, G.R., Malhotra, A. & Müller, R. Mechanical Stimuli in the Local In Vivo Environment in Bone: Computational Approaches Linking Organ-Scale Loads to Cellular Signals. Curr Osteoporos Rep 16, 395–403 (2018). https://doi.org/10.1007/s11914-018-0448-6

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