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Differential Effects of PPAR-γ Activation vs. Chemical or Genetic Reduction of DPP-4 Activity on Murine Bone Quality

This study characterized the effects of two anti-diabetic drugs, a thiazolidinedione
(TZD) and a Dipeptidyl Peptidase-4 (DPP-4) inhibitor on bone quality in a glucose
intolerant mouse model. Bone quality in a DPP-4 -/- mouse model was also examined. Bone
quality was evaluated through densitometry, mechanical testing and techniques to assess
remodeling, structural and mineral properties.
TZD treatment negatively affected trabecular mechanical properties in male, female
and ovariectomized female (OVX) mice. Male mice exhibited the greatest effect due to TZD
treatment with reduced vertebral vBMD, trabecular structure and bone formation. DPP-4 inhibitor treatment improved vertebral vBMD and trabecular architecture in female mice but improvements were lost in females following OVX. Male, female and OVX mice
experienced increased trabecular mineralization due to DPP-4 inhibitor treatment. Genetic inactivation of DPP-4 did not produce a major bone phenotype in male and female mice but lead to reduced femoral geometry and mechanics in OVX mice.

Identiferoai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/25738
Date07 January 2011
CreatorsKyle, Kimberly Anne
ContributorsGrynpas, Marc D.
Source SetsUniversity of Toronto
Languageen_ca
Detected LanguageEnglish
TypeThesis

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