The important role the meniscus plays in the normal functioning of the knee joint is now acknowledged: damage to the tissue, as frequently occurs in knee injuries, leads to degeneration of the articular cartilage. Yet, the literature on the biology of the meniscus is sparse and very little is known about the phenotype of the meniscal fibrochondrocyte. Type VI collagen is a multidomain adhesion protein that is enriched in the meniscus and our preliminary data suggests it plays important roles in the maintenance of tissue architecture, as an attractant in cell migration and as an intermolecular adhesion protein in the extracellular matrix. The pattern of gene expression and the spatial distribution of selected proteins in the matrix will be defined: (a) by assessing the relative amounts of mRNA for fibrillar collagens and other matrix proteins extracted from meniscus, articular cartilage and patellar tendon, and cells derived from these tissues and cultured in vitro for varying periods of time; (b) by immunolocalization of fibrillar collagens and matrix protein in meniscal tissue. The capacity of type VI collagen to function as a haptotactic attractant for meniscal fibrochondrocytes will be assessed in vitro in Boyden chambers. We hypothesize that changes in the structure/function and distribution of type VI collagen occur in degeneration of the meniscus. In an in vitro model, we will expose type VI collagen to metal ions and investigate the changes in the adhesive properties of the molecule. In a series of collaborative studies, we will establish changes in type VI collagen that occur in vivo in dogs that have undergone ACL transection. Collectively, these studies will provide new and important information on the nature of the cells in the meniscus and the role of the cells and adhesion protein in meniscal repair and destruction.
