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Mitigation of Bone Loss and Augment of Anabolic Adaptation by Physiological Dynamic Fluid Flow Stimulation

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dc.contributor.advisor Qin, Yi-Xian en_US
dc.contributor.author Hu, Minyi en_US
dc.contributor.other Department of Physiology and Biophysics en_US
dc.date.accessioned 2013-05-24T16:38:19Z
dc.date.accessioned 2015-04-24T14:47:50Z
dc.date.available 2013-05-24T16:38:19Z
dc.date.available 2015-04-24T14:47:50Z
dc.date.issued 2012-12-01 en_US
dc.identifier.uri http://hdl.handle.net/1951/60264 en_US
dc.identifier.uri http://hdl.handle.net/11401/71530 en_US
dc.description 136 pg. en_US
dc.description.abstract Novel modalities with strong translational potential to prevent osteoporosis are urgently called for, as osteoporosis strikes the society with high incidences of disease-related fractures and excessive medical costs. While bone fluid flow (BFF) regulates bone adaptation, intramedullary pressure (ImP) can initiate BFF and influence osteogenic signals. To establish the translational potential, a non-invasive intervention with direct ImP-coupled BFF can help develop new non-pharmaceutical treatments for osteopenia/osteoporosis. The overall objective of this dissertation was to investigate the effects of a novel, non-invasive dynamic hydraulic stimulation (DHS) on skeletal regulatory responses at the tissue, cellular, and molecular levels. The global hypothesis was that DHS mediates ImP-induced regulation of BFF and promotes osteogenic adaptation, which in turn mitigates bone deterioration under disuse condition. This hypothesis was tested with four specific aims: 1) to investigate the ability of DHS to induce ImP with minimal bone strain as a loading dependence matter, and to determine the optimized DHS in bone, 2) to evaluate the effects of optimized DHS on skeletal tissue adaptation under functional disuse condition, 3) to evaluate the effects of optimized DHS on bone marrow mesenchymal stem cell (MSC) population, 4) to elucidate the alterations of the gene expressions of osteogenic growth factors and transcription factors in response to DHS. Immediate ImP induction was observed in the in vivo rat tibiae in response to DHS. Induced ImP (peak-to-peak) values were in a nonlinear fashion over the loading frequencies (1~10 Hz), which peaked at 2 Hz. Oscillatory DHS at various loading frequencies generated minimal bone strain. Furthermore, trabecular bone quantities and microstructural properties, as well as dynamic remodeling processes of the loaded tibiae in hindlimb suspended rats were evaluated using microCT and histomorphometry analyses. Significant improvements by oscillatory DHS on trabecular bone structural properties and bone formation indices were shown. These data strongly suggest that oscillatory DHS may regulate the tissue fluid dynamics, which serves critically in bone adaptation. Finally, longitudinal evaluations of bone marrow MSC population and osteogenic gene expressions demonstrated the effects of DHS on bone at the cellular and molecular levels, as well as their contributions to mitigate phenotypic disuse bone loss. These results clearly imply the ability of DHS as an effective, non-invasive intervention for potential osteopenia and osteoporosis treatments. en_US
dc.description.sponsorship This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree. en_US
dc.format Monograph en_US
dc.format.medium Electronic Resource en_US
dc.language.iso en_US en_US
dc.publisher The Graduate School, Stony Brook University: Stony Brook, NY. en_US
dc.subject.lcsh Physiology--Biophysics--Biomedical engineering en_US
dc.title Mitigation of Bone Loss and Augment of Anabolic Adaptation by Physiological Dynamic Fluid Flow Stimulation en_US
dc.type Dissertation en_US
dc.mimetype Application/PDF en_US
dc.contributor.committeemember White, Thomas W.El-Maghrabi, Raafat en_US
dc.contributor.committeemember Sun, Hui (Herb) B.. en_US

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