The effect of fluid shear stress on growth plate chondrocytes
Denison, Tracy Adam
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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.