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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/18833

Title: Calcium Regulates Cyclic Compression-induced Early Changes In Chondrocytes During In Vitro Tissue Formation
Authors: Raizman, Igal
Advisor: Kandel, Rita A.
Department: Laboratory Medicine and Pathobiology
Keywords: Mechanotransduction
Chondrocytes
Issue Date: 15-Feb-2010
Abstract: A single application of cyclic compression to bioengineered cartilage improves tissue formation through cell shape changes that are mediated by α5β1 integrin and membrane-type metalloprotease (MT1-MMP). To determine if this response is controlled by calcium, we investigated how calcium regulated cell shape changes, MT1-MMP and integrin activity in response to stimulation. Stimulation-induced changes in cell shape and MT1-MMP expression were abolished with chelation of extracellular calcium, and reinstated with its re-introduction. Spreading and retraction were inhibited by blocking the stretch-activated and L-Type voltage-gated channels, respectively; channel blocking also inhibited MT1-MMP upregulation. Channels’ role was confirmed through treatment with calcium A23187 ionophore, which alleviated the effects of channel blocking. Calcium regulated the integrin-mediated signalling pathway, which was facilitated through the kinase Src. Both calcium- and integrin-mediated pathways converged on activating ERK in response to stimulation. Understanding the molecular mechanisms regulating chondrocyte mechanotransduction may lead to the development of improved bioengineered cartilage.
URI: http://hdl.handle.net/1807/18833
Appears in Collections:Master
Department of Laboratory Medicine and Pathobiology - Master theses

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