Institute of Genetic Medicine

Skeletal Diseases

Skeletal Diseases

We're investigating the genetics behind foetal bone development in an attempt to understand the factors that lead to conditions like dwarfism.


During foetal bone growth, cartilage cells in the growth plate undergo a co-ordinated, controlled process of:

  • proliferation (increase in number)
  • hypertrophy (increase in size)
  • apoptosis (programmed cell death)

Cartilage cell proliferation and hypertrophy is vital for correct long bone growth.

Death of fully-grown cartilage cells is critical in transition to formation of bone.

Disruptions to these processes lead to growth plate abnormalities. The result is a group of genetic diseases known as skeletal dysplasias.

Short-limb dwarfism is the predominant characterisation in these circumstances.

We look at the genetic factors that contribute to skeletal dysplasias.
We look at the genetic factors that contribute to skeletal dysplasias.

The scientific story

During growth plate maturation, cartilage cells synthesise and secrete structural proteins.

Mutant forms of these proteins cause stress on the process and induce unfolded protein response (UPR).

The UPR is a sophisticated quality control system that aims to reduce this stress. It activates different pathways mediated by three receptors, IRE1, ATF6 and PERK.

If this is not achieved, prolonged stress can result in the body killing off cartilage cells.

Mouse models

We have used mouse models to get a better understanding of these processes. We have sought answers on whether UPR helps protect cartilage cells or causes more distress.

Answering this fundamental question will help explain initiation and progression of skeletal dysplasias.

It will provide essential insight into disease mechanisms in many different diseases.