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Errata tipped inside back end paper. / Bibliography: leaves 150-190. / vi, 190 leaves : ill. (chiefly col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Insulin-like growth factors (IGFs) and inflammatory cytokines (e.g. IL-1) affect cartilage metabolism in opposite ways. The actions of IGFs in biological systems are modulated by locally produced IGF binding proteins (IGFBPs). This thesis investigated the effects of the IGFs and inflammatory cytokines on IGFBPs produced by chondrocytes and the subsequent interplay of these factors on proteoglycan production in vitro. To do this, a primary culture of ovine articular chondrocytes was used as an in vitro experimental model system. It was concluded that the IGFBP-5-mediated decrease in proteoglycan synthesis could be a relevant in vivo mechanism by which IL-1 exerts its catabolic effect and disturbs the balance between the synthesis and degradation of cartilage matrix macromolecules in pathological conditions. / Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine, 1998?

Indiana University-Purdue University Indianapolis (IUPUI) / Articular cartilage is subjected to dynamic mechanical loading during normal daily activities. This complex mechanical loading, including cell deformation and interstitial fluid flow, affects chondrocyte mechano-chemical signaling and subsequent cartilage homeostasis and remodeling. Focal adhesion kinase (FAK) and Src are known to be main mechanotransduction proteins, but little is known about the effect of mechanical loading on FAK and Src under its varying magnitudes and types. In this study, we addressed two questions using C28/I2 chondrocytes subjected to the different types and magnitudes of mechanical loading: Does a magnitude of the mechanical loading affect activities of FAK and Src? Does a type of the mechanical loading also affect their activities? Using fluorescence resonance energy transfer (FRET)-based FAK and Src biosensor in live C28/I2 chondrocytes, we monitored the effects of interstitial fluid flow and combined effects of cell deformation/interstitial fluid flow on FAK and Src activities. The results revealed that both FAK and Src activities in C28/I2 chondrocytes were dependent on the different magnitudes of the applied fluid flow. On the other hand, the type of mechanical loading differently affected FAK and Src activities. Although FAK and Src displayed similar activities in response to interstitial fluid flow only, simultaneous application of cell deformation and interstitial fluid flow induced differential FAK and Src activities possibly due to the additive effects of cell deformation and interstitial fluid flow on Src, but not on FAK. Collectively, the data suggest that the intensities and types of mechanical loading are critical in regulating FAK and Src activities in chondrocytes.