The ability of tissues to adapt to the mechanical environment is a remarkable feature of the skeleton. Although the mechano-regulation process is very complex, several mechano-regulation theories for musculo-skeletal tissues have successfully predicted the tissue differentiation and remodelling process in various scenarios with reasonable accuracy (1,2); but how did mechano-regulated bone differentiation emerge in evolution? Early vertebrates, like cartilaginous fishes, could modulate their tissues to the mechanical environment and it is likely that evolution worked with the regulatory genes for skeletal tissues, rather than changes in structural genes, i.e. adapting skeletal tissues to the local conditions rather than involving major changes in cells or tissue types (3).

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