Cartilage facilitates articulations between skeletal elements (e.g., appendicular joints), provides a transitional matrix during skeletal growth (e.g., growth plate) and protects and supports nonskeletal tissues and organs (e.g., trachea). Since the major organic constituent of cartilage is collagen, the long range goal of the proposed research are directed toward an understanding of what governs the biosynthesis, posttranslational modifications, extracellular interactions and phenotypic expression of cartilage collagens in normal and disease states. The proposed experiments will study the structure and processing of a minor cartilage collagen (type XI), the pericellular localization of cartilage collagens in suspension cultures of chondrocytes, the absolute rates of synthesis and secretion of the cartilage collagens under various metabolic conditions, and the role of calcium in determining the type of collagen synthesized. These studies will be performed using in vitro metabolic labeling of cultures of chick embryo sternal cells. The newly synthesized cartilage collagen precursors will be identified (where possible) by immunoprecipitation or immunoblotting using monoclonal antibodies, purified by a combination of salt precipitations, ion-exchange and gel filtration chromatography, analyzed by polyacrylamide gel electrophoresis and quantitated by densitometry. The calcium studies will be performed with state-of-the-art fluorometric techniques and an electroporation device. These investigations will further our knowledge of cartilage collagen structure and metabolism, and provide a framework for an understanding of the basic mechanisms which underlie normal skeletal growth and development.
| Clark, C C; Iannotti, J P; Misra, S et al. (1994) Effects of thapsigargin, an intracellular calcium-mobilizing agent, on synthesis and secretion of cartilage collagen and proteoglycan. J Orthop Res 12:601-11 |
| Clark, C C; Richards, C F; Iozzo, R V (1991) Post-translational alterations in newly synthesized cartilage proteoglycans induced by the glutamine analogue 6-diazo-5-oxo-L-norleucine. Time course of inhibition and recovery. Biochem J 273(Pt 2):283-8 |
