There is a lack of a clear understanding of the contribution of specific matrix components to the mechanical properties of articular cartilage. The investigator has developed a cell line which will synthesize a mechanically testable cartilaginous matrix and have identified several variants of this line which synthesize an abnormal proportion of various matrix components, including chondroitin sulfate, aggrecan, and type IX collagen. The investigator proposes to use these mutant cell lines to examine how alterations in structures affect the assemble of the matrix and the mechanical properties of the resulting tissue.
Three specific aims are proposed. 1) Examine the contribution of the sulfate moiety on the proteoglycans to tissue formation and function with a mutant chondrocyte cell line which makes an undersulfated proteoglycan. 2) Examine the role of the chondroitin sulfate glycosaminoglycan component of proteoglycans to tissue formation and function by decreasing the amount of chondroitin sulfate on the proteoglycan with beta-xyloside inhibition. 3) Examine the effects of changing the relative proportions of selected matrix macromolecules on matrix assembly and mechanical properties. The matrices formed will be analyzed to determine proteoglycan synthesis, content and structure and aggregation, collagen content and type, morphology, immunolocalization, and mechanical properties.
|King, Karen B; Kimura, James H (2003) The establishment and characterization of an immortal cell line with a stable chondrocytic phenotype. J Cell Biochem 89:992-1004|