Cartilage tissue provides compressive resistance in diarthrodial joints, and has
been shown to be regulated by mechanical signals, in particular with regard to production
of extracellular matrix proteins. However, less is understood about how chondrocytes in
regions not solely purposed to provide compressive resistance may also be affected by
mechanical forces. The growth plate is a small layer of cartilage that functions to
facilitate longitudinal growth of the long bones from in utero through post-adolescent
development. The growth plate maintains distinct regions of chondrocytes at carefully
regulated stages of endochondral ossification that are in part characterized by their
morphology and differential responsiveness to vitamin D metabolites. Understanding if
mechanical cues could be harnessed to accelerate or delay the process of endochondral
ossification might be beneficial for optimizing tissue engineering of cartilage or
osteochondral interfaces. This study focused on three aims to provide a basis for future
work in this area: 1) Develop a cell line culture model useful for studying growth plate
chondrocytes, 2) Determine the response of primary growth plate chondrocytes and the
cell line model to fluid shear stress, and 3) determine if expression of integrin beta 1 is
important for the observed responses to shear stress. The findings of this study suggest
that inorganic phosphate can promote differentiation in coordination with the
24,25(OH)2D3 metabolite of vitamin D, and that fluid shear stress generally inhibits
differentiation and proliferation of growth plate chondrocytes in part through an integrin
beta 1 mediated pathway.
| Identifer | oai:union.ndltd.org:GATECH/oai:smartech.gatech.edu:1853/29603 |
| Date | 30 June 2009 |
| Creators | Denison, Tracy Adam |
| Publisher | Georgia Institute of Technology |
| Source Sets | Georgia Tech Electronic Thesis and Dissertation Archive |
| Detected Language | English |
| Type | Dissertation |
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