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ERC

MechJointMorph Report Summary

Project ID: 336306
Funded under: FP7-IDEAS-ERC
Country: United Kingdom

Mid-Term Report Summary - MECHJOINTMORPH (The role of mechanical forces induced by prenatal movements in joint morphogenesis)

The aim of this project is to gain a better understanding of how our joints attain their shapes during prenatal development, with particular focus on the interplay between the genetically determined biological growth and the contribution of mechanobiological growth directed by mechanical forces due to fetal movements. The main achievements of the project to date are as follows:

- The differential effects of absent movement on major joints in the mouse embryo (hip, knee, shoulder and elbow) have been quantified using 3D imaging and novel image registration techniques for one timepoint (embryonic day (e)14.5) (work in preparation for publication)
o We have demonstrated that the shape of the hip joint develops normally in immobile mouse embryos, meaning that the hip of the muscleless limb mouse is not a suitable model system for hip dysplasia. Therefore, more affected joints such as the elbow, will be used as the model for hip dysplasia for this research, in addition to the chick model system
o Current work is gathering data for all major joints for the complete timespan of relevant developmental time, from from e13.5 to P0

- The key timepoints for the emergence of joint shape in the chick model system have been identified as being the two day period from e5 to e6. Immobilising a chick embryo for this two day period has the same effects on hip joint shape as immobilising continuously from e3 to e8 (work in preparation for publication).
- It is possible to mitigate the effects of embryonic immobility on joint shape by artificially applying movement at the developing joint in the chick model system (work in preparation for publication). Future work will investigate the phenomenon for a mammalian model system (mouse).

- A novel system for in vitro culture of embryonic limb explants has been implemented, enabling us to show that a movement regime similar to that which occurs during development leads to optimal shape development of the joint (work under review). Current work is using the same system to block mechanosensitive pathways in order to assess their role in the mechanoregulation of morphogenesis.

- The first mechanobiological simulation of prenatal joint shape morphogenesis has been proposed and tested (Giorgi et al., 2014), and shown to be able to predict normal and abnormal hip joint development (Giorgi et al., 2015). This work proposed the first mechanoregulation theory for the growth of developing cartilage. Work planned for 2017 will build upon the model to adapt it for real joint shapes (from WP1) and to include more realistic biological growth parameters (e.g., proliferation, migration)

Contact

Shaun Power, (Research Services Manager)
Tel.: +44 207 594 8773
Fax: +44 207 594 8609
E-mail
Record Number: 195401 / Last updated on: 2017-03-13
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