Abstract
While the phenomena of bone adaption to mechanical loading has been long observed, the mechanisms governing bone mechanotransduction during health and disease are not well understood. Our multidisciplinary experimental and computational research strives to enhance understanding of bone mechanobiology, and in particular how this process is affected at the onset of osteoporosis. We have provided an enhanced understanding of bone cell mechanosensation. We have characterised the local mechanical environment of MSCs, osteoblasts and osteocytes in vivo. Most importantly, we have discovered that the matrix composition, expression of mechanosensors and the mechanical environment of osteocytes is altered during osteoporosis. Interestingly, a mechanobiological response restores the homeostatic mechanical environment of the cells in the longer term. Our recent in vitro studies have revealed that estrogen withdrawal from bone cells alters calcium signalling, mineralisation, biochemical responses and osteogenic gene expression when these cells are exposed to an applied fluid shear stress. Our ongoing research is investigating mechanobiology-based therapeutic approaches for treatment of bone pathologies, by (1) targeting mechanoregulatory signalling pathways and (2) developing in vitro tissue regeneration strategies that seek to optimise the mechanical environment (through matrix stiffness, bioreactors) to stimulate osteogenesis.
