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Defining the balance between regeneration and pathological ossification in skeletal muscle

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posted on 31.03.2017 by Owen Davies, Yang Liu, Darren Player, Neil Martin, L.M. Grover, Mark Lewis
Heterotopic ossification (HO) is characterised by the formation of bone at atypical sites. This type of ectopic bone formation is most prominent in skeletal muscle, most frequently resulting as a consequence of physical trauma and associated with aberrant tissue regeneration. The condition is debilitating, reducing a patient’s range of motion and potentially causing severe pathologies resulting from nerve and vascular compression. Despite efforts to understand the pathological processes governing HO, there remains a lack of consensus regarding the micro-environmental conditions conducive to its formation, and attempting to define the balance between muscle regeneration and pathological ossification remains complex. The development of HO is thought to be related to a complex interplay between factors released both locally and systemically in response to trauma. It develops as skeletal muscle undergoes significant repair and regeneration, and is likely to result from the misdirected differentiation of endogenous or systemically derived progenitors in response to biochemical and/or environmental cues. The process can be sequentially delineated by the presence of inflammation, tissue breakdown, adipogenesis, hypoxia, neo-vasculogenesis, chondrogenesis and ossification. However, exactly how each of these stages contributes to the formation of HO is at present not well understood. Our previous review examined the cellular contribution to HO. Therefore, the principal aim of this review will be to comprehensively outline changes in the local tissue micro-environment following trauma, and identify how these changes can alter the balance between skeletal muscle regeneration and ectopic ossification. An understanding of the mechanisms governing this condition is required for the development and advancement of HO prophylaxis and treatment, and may even hold the key to unlocking novel methods for engineering hard tissues.

Funding

EPSRC E-TERM Landscape Fellow, EP/I017801/1

History

School

  • Sport, Exercise and Health Sciences

Published in

Frontiers in Physiology

Citation

DAVIES, O.G. ... et al., 2017. Defining the balance between regeneration and pathological ossification in skeletal muscle. Frontiers in Physiology, 8:194, doi: 10.3389/fphys.2017.00194

Publisher

Frontiers Media (© Davies, Liu, Player, Martin, Grover and Lewis)

Version

VoR (Version of Record)

Publisher statement

This work is made available according to the conditions of the Creative Commons Attribution 4.0 International (CC BY 4.0) licence. Full details of this licence are available at: http://creativecommons.org/licenses/ by/4.0/

Acceptance date

15/03/2017

Publication date

2017-04-03

Notes

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

ISSN

1664-042X

Language

en

Licence

Exports