Bone ensures it is sufficiently robust to withstand habitual levels of mechanical loading without unsustainable levels of damage by adapting to the strain environment engendered by normal activity. This process becomes less effective with age when loss of bone tissue occurs despite continued activity. Here I report experiments to investigate the (re)modelling response to a loading challenge in both trabecular and cortical bone in young adult and aged male and female mice against different levels of background activity. Loading-related increases in trabecular and cortical bone in response to short periods of unilateral non-invasive axial loading of the tibia were compared between young and aged male and female mice. In trabecular bone, increase in connectivity was impaired with age. In cortical bone the increase in new bone formation was less and endosteal instead of periosteal. Remarkably both the size and location of this response in the cortices of aged animals could be “rescued” by inducing disuse in the same limb by sciatic neurectomy. Conversely, concurrent treadmill exercise, while having potentially beneficial systemic effects, did not enhance the adaptive response to loading. Studies aimed at identifying the stage of the adaptive response to loading where aged animals first digressed from young adults showed that strain-related sclerostin down regulation, which occurs in osteocytes 12-24 hours after loading, was unaffected by age. However, ageing was associated with a lower increase in active periosteal osteoblasts. In vitro, primary osteoblast-like cells derived from long bones of young and aged mice showed age-related sex-specific alterations in their responses to strain 1 hour following strain. In cells from aged female mice, a cell cycle arrest during proliferation was observed 24 hours after strain. Microarray analysis of tibiae in vivo showed that over 150 genes regulating the cell cycle were altered with age.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:601212 |
| Date | January 2013 |
| Creators | Meakin, Lee Bryan |
| Contributors | Price, Joanna |
| Publisher | University of Bristol |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1983/4eddf8e6-23a6-478c-a9ed-37c9097a932e |
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