Author's Department/Program
Biomedical Engineering
Language
English (en)
Date of Award
January 2009
Degree Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Chair and Committee
Matthew Silva
Abstract
Woven and lamellar bone formation can be stimulated using mechanical loading. Woven bone forms rapidly in response to damaging loading in a disorganized manner with low mineral density. In contrast, lamellar bone formation can be induced in the absence of damage, and is characterized by its slow, organized deposition and high density. In this dissertation, we first examined the molecular response to woven and lamellar bone formation using damaging and non-damaging dynamic loading protocols, respectively. We observed a significant increase in gene expression related to angiogenesis, cell proliferation and osteogenesis prior to woven bone formation, with significantly lower levels of expression associated with lamellar bone formation. To fully characterize the molecular responses of woven and lamellar bone we used a whole genome microarray. The micorarray results brought to light many inflammatory factors not previously investigated in our model, expanded previous findings about angiogenesis, and strengthened our understanding of the role of osteogenic pathways. Our investigations suggested that angiogenesis is required for successful woven bone formation. We used several angiogenic inhibitors, but were unable to prove the dependence of woven bone formation on angiogenesis. Finally, we sought to separate the effects of static and dynamic strains on bone formation. These findings demonstrate that in the absence dynamic strain, bone damage triggers a woven bone response that leads to a functional repair of whole-bone strength. Overall, the work done in this thesis has enhanced our understanding of bone formation. Future studies will expand on the microarray findings and clarify the role of angiogenesis in woven bone formation.
Recommended Citation
McKenzie, Jennifer, "Investigations into the Ulnar Response to Mechanical Stimuli Activating Lamellar and Woven Bone Formation" (2009). All Theses and Dissertations (ETDs). 417.
https://openscholarship.wustl.edu/etd/417
Comments
Permanent URL: http://dx.doi.org/10.7936/K7B85648