|Title:||The role of endogenous glucocorticoid actions in cartilage|
|Publisher:||University of Sydney|
Faculty of Medicine
Concord Clinical School.
|Abstract:||States of glucocorticoid excess are associated with defects in chondrocyte function. Most prominently there is a reduction in linear growth, and delayed healing of fractures and attenuated cartilage degradation in arthritis that require chondrocyte functions also occur. In contrast, little is known about the role of endogenous glucocorticoid actions in chondrocyte function. As gluco¬corticoids exert their cellular actions through the glucocorticoid receptor (GR), we aimed to elucidate the role of endogenous glucocorticoids in chondrocyte function in vivo through a chondrocyte-specific GR knockout (chGRKO) mouse model. Results showed that: 1) chGRKO mice exhibit normal postnatal skeletal growth compared to control mice at 2, 4, and 10-weeks of age; 2) Chondrocyte-specific GR deletion delays metaphyseal fracture healing of tibia; 3) Chondrocyte-specific GR deletion exaggerates K/BxN serum-induced arthritis, associated with prominent inflammatory activity and increased bone destruction; 4) Endogenous GC signalling disruption in mature osteoblasts attenuates arthritis not only in K/BxN serum-induced arthritis but also in collagen-antibody-induced arthritis. Overall, although often ignored, chondrocytes do play an important role in mediating the effects of endogenous GCs in fracture healing and inflammation. These findings could also provide the basis for novel therapeutic strategies for the optimal clinic use of GCs.|
|Access Level:||Access is restricted to staff and students of the University of Sydney . UniKey credentials are required. Non university access may be obtained by visiting the University of Sydney Library.|
|Rights and Permissions:||The author retains copyright of this thesis. It may only be used for the purposes of research and study. It must not be used for any other purposes and may not be transmitted or shared with others without prior permission.|
|Type of Work:||PhD Doctorate|
|Type of Publication:||Doctor of Philosophy Ph.D.|
|Appears in Collections:||Sydney Digital Theses (University of Sydney Access only)|
|TU Jinwen - Final Thesis.pdf||25.63 MB||Adobe PDF|
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