Our previous studies of the epiphyseal growth cartilage have served to focus attention on the relationship between oxidative metabolism and the initiation of mineralization. These studies showed that aside from normal respiratory activities there was evidence of non-mitochondrial oxidative metabolism. Moreover, preliminary investigations indicated that there was evidence of shunt activity and lipid peroxidation in the growth cartilage. In skeletal and dental tissues, a developmental role for the abrupt changes in oxidative metabolism documented during chondrocyte maturation and subsequent mineralization is postulated. The proposed experiments examine the status of non-mitochondrial oxygen metabolism both in situ in the growth plate and in vitro employing a mineralizing chondrocyte culture system. In particular, this study focuses on mechanisms of matrix vesicle biogenesis and expression of collagenous and non-collagenous proteins in relationship to non-mitochondrial oxidative metabolism.
Four Specific Aims are proposed. The first is to map lipid peroxidation and oxygen radical degradation in the growth plate in relationship to maturation of the chondrocyte. Second, we will explore the effects of lipid peroxidation on matrix vesicle biogenesis in cultured chondrocytes. The third Specific Aim will examine the impact of oxygen radical species on expression and function of collagenous and non-collagenous proteins. Finally, the last Specific Aim will probe a possible mechanism for matrix vesicle biogenesis implicating non-mitochondrial oxidative metabolism in the selection of chondrocyte membrane segments for vesiculation.
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