The importance of foetal movement for co-ordinated cartilage and bone development in utero : clinical consequences and potential for therapy

Bone Joint Res. 2015 Jul;4(7):105-16. doi: 10.1302/2046-3758.47.2000387.

Abstract

Construction of a functional skeleton is accomplished through co-ordination of the developmental processes of chondrogenesis, osteogenesis, and synovial joint formation. Infants whose movement in utero is reduced or restricted and who subsequently suffer from joint dysplasia (including joint contractures) and thin hypo-mineralised bones, demonstrate that embryonic movement is crucial for appropriate skeletogenesis. This has been confirmed in mouse, chick, and zebrafish animal models, where reduced or eliminated movement consistently yields similar malformations and which provide the possibility of experimentation to uncover the precise disturbances and the mechanisms by which movement impacts molecular regulation. Molecular genetic studies have shown the important roles played by cell communication signalling pathways, namely Wnt, Hedgehog, and transforming growth factor-beta/bone morphogenetic protein. These pathways regulate cell behaviours such as proliferation and differentiation to control maturation of the skeletal elements, and are affected when movement is altered. Cell contacts to the extra-cellular matrix as well as the cytoskeleton offer a means of mechanotransduction which could integrate mechanical cues with genetic regulation. Indeed, expression of cytoskeletal genes has been shown to be affected by immobilisation. In addition to furthering our understanding of a fundamental aspect of cell control and differentiation during development, research in this area is applicable to the engineering of stable skeletal tissues from stem cells, which relies on an understanding of developmental mechanisms including genetic and physical criteria. A deeper understanding of how movement affects skeletogenesis therefore has broader implications for regenerative therapeutics for injury or disease, as well as for optimisation of physical therapy regimes for individuals affected by skeletal abnormalities. Cite this article: Bone Joint Res 2015;4:105-116.

Keywords: FADS; endochondral ossification; immobilisation; joint cavitation; mechanoregulation; skeletal development.

Publication types

  • Review

Grant support

CAS is supported by a studentship from the Irish Research Council. R. A. Rolfe was supported by a studentship from Trinity College Dublin (Innovation Bursary). P. Murphy reports receipt of a grant from the Wellcome Trust to complete this study. All three authors have received financial assistance from the Trinity College Travel grant award scheme.