Thomas Martin Hering

The cartilage proteoglycan aggregate is a unique configuration of macromolecules which along with type II collagen and a number of accessory molecules confers upon cartilage its special biomechanical properties. It is composed of chondroitin sulfate proteoglycan monomers bound into very large aggregates with hyaluronate, an interaction which is stabilized by the binding of a third component, the link protein, a 45-50 kDa glycoprotein which is bivalent in that it has binding sites for both the proteoglycanhyaluronic acid binding region (HABR) and for hyaluronate. In osteoarthritis there is a loss of proteoglycans from cartilage resulting from disruption of the normal aggregate structure.
Our present objective is to use recombinant (DNA) techniques to determine mechanisms for intermolecular interactions occurring between the 3 components of the proteoglycan aggregate. We have isolated cDNA clones for the bovine link protein and large proteoglycan and experiments are in progress to alter by site-directed mutagenesis specific regions of the link protein or the proteoglycan HABR, to express mutagenized clones as protein and determine functionality in specific binding assays.

Additional studies in progress are concerned with isolation and characterization of cDNA clones for novel chondrocyte proteins involved in the osteoarthritic process and cartilage repair.

FIRST Award, National Institutes of Health, 1991