We are investigating whether epigenetic marks, such as DNA methylation early in life, relate to intrauterine growth, placental calcium transport and postnatal skeletal development.

The potential of developmental environmental modulation to alter epigenetic marking, and thereby offspring phenotype, has been demonstrated convincingly in animal experiments at the Institute of Developmental Sciences. In parallel human studies, we have observed associations between methylation at sites in the promoter regions of retinoid-X-receptor A, endothelial nitric oxide synthase, CDKN2A, and offspring bone mass and body composition

Epigenetic Ingenuity Pathway Analysis: MeDIP-CHIP

  • Development: Regulation of epithelial-to-mesenchymal transition (EMT)
  • Apoptosis and survival: Endoplasmic reticulum stress response pathway
  • Cytoskeleton remodelling: Role of Activin A in cytoskeleton remodelling
  • Development: FGF2-dependent induction of EMT
  • NGF activation of NF-kB

Molecular and cellular pathways identified from MeDIP-CHIP array for further characterisation

Working with collaborators at the Institute of Developmental Sciences, University of Southampton, the University of Bristol, and King’s College London, we are exploring epigenetic signals in relation to skeletal development across the lifecourse. We have a well-established discovery pipeline from genome wide to candidate and functional validation, using observational cohorts such as Southampton Women’s Survey in early life, and Hertfordshire Cohort in older age, together with unique opportunities to test identified targets in the context of randomised controlled trials such as MAVIDOS.

In addition to increased mechanistic understanding, these studies have the potential to identify epigenetic signals that may be used as early biomarkers of later adverse bone health, enabling the targeting of lifestyle interventions (for example maternal vitamin D or PUFA supplementation) to individuals at the greatest risk of future fracture.