Because bone's ECM and its modifications are determined by events at molecular, cellular, and tissue levels, our research spans these natural length scales in bone. Using approaches from the fields of mechanics, material science, biochemistry and cell biology we create and use experimental model systems to investigate the mechanics and biology of bone fragility associated with aging, osteoporosis and diabetes.
At the molecular level, we have identified the age-related accumulation of advanced glycation end-products (AGEs) in type I collagen of bone and are currently investigating the mechanisms by which it accumulates and modifies the energy dissipation characteristics of bone. In particular, studies are ongoing on naturally aged and Insulin-like Growth Factor-I (IGF-I) deficient and osteocalcin knock-out mice to determine if IGF-I and osteocalcin play a role in controlling the AGEs accumulation in bone.
At the cellular level, we work with adult human mesenchymal stem cells (hMSCs) and osteoclasts to study factors affecting bone quantity and its interaction with bone quality. The acquisition of bone is investigated from a mechanobiology perspective in which the role of mechanics in determining stem cell fate is of particular interest. Osteoclasts or the principal bone resorbing cells are being investigated to ascertain whether the modification of bone quality by mechanical damage or by protein modification enhances bone resorption affecting the amount of bone.
At the tissue level, the effect of AGEs, non-collagenous matrix proteins, mechanical damage and multiaxial cyclic loading on bone fracture are being investigated. Using a combination of fracture mechanics approach, multiphoton confocal imaging, laser microdissection and proteomics we are investigating the biomolecular basis of osteoporotic and diabetic fractures.