Studies on chondroadherin-an extracellular matrix leucine-rich repeat protein

Abstract: This thesis describes chondroadherin, one of the leucine-rich repeat proteins in the extracellular matrix (ECM) of cartilage. Chondroadherin defines a subgroup of its own by not having an N-terminal extension, having a different cysteine pattern and by being devoid of carbohydrate substitutions. Here we show that chondroadherin also have a different exon-intron organization and chromosomal localization compared to the other closest related family members. Chondroadherin is mainly found close to the chondrocytes and it has previously been shown to bind chondrocytes. In this thesis we show that chondroadherin interacts with collagen type II. This is shown both in material extracted from articular cartilage and in vitro. The interaction between chondroadherin and collagen type II was characterized by plasmon resonance in the BIAcore and by electron microscopy. Chondroadherin is shown to interact with collagen type II at two sites. The collagen in the tissue extracted material was mainly monomeric suggesting that chondroadherin might have a role in regulation of collagen fibril formation. We also identify a new interaction between chondroadherin and cartilage oligomeric matrix protein (COMP). Chondroadherin binds to the C-terminal globular domain of COMP, the interaction is dependent on zinc ions. The interaction between chondroadherin and COMP was shown to inhibit COMP binding to collagen. One suggested function of COMP is to bind several collagen molecules and bring them close to each other to facilitate fibril formation. Chondroadherin might regulate collagen fibril formation by binding COMP thus inhibiting its binding to collagen.