Role of Proteoglycans in Osteoarthritis

Abstract

The articular cartilage covers the end of the long bones and ensures frictionless motion of the joints. Chondrocytes produce and maintain in a homeostatic equilibrium a large amount of extracellular matrix (ECM), thereby ensuring the cartilage function in locomotion and the absorption of biomechanical stress throughout life. To achieve this, chondrocytes are extremely sensitive to mechanical stress and injury signals and can rapidly adapt their metabolic activity ultimately ensuring that remodeling and repair of the tissue follow injury.

Proteoglycans as one of the main components of the ECM have diverse functions in the cartilage. They bind water and provide the basis for absorbing high compressive loads. Additionally, they bind cytokines, chemokines, growth factors, and morphogens, thereby protecting these factors against proteolysis and/or acting as a depot of regulatory factors when matrix degradation occurs. They also modulate signaling pathways and create morphogen gradients by immobilization of ligands in the ECM and regulation of the turnover of ligands. The extracellular domains of proteoglycans can be shed from the cell surface, generating soluble decoy receptors, and they can act as co-receptors for various tyrosine-kinase-type growth factor receptors. Furthermore, they can act as endocytic receptors and contribute to the clearance of bound ligands and cooperate with integrins and other cell adhesion receptors to facilitate cell attachment, cell–cell interactions, and cell motility.

Given these important roles of proteoglycans in regulating cell functions, it is well understandable that loss of ECM and degradation of proteoglycans during OA induce severe changes in cartilage homeostasis. The following review will discuss the role of different proteoglycans in the aforementioned processes with special emphasis on the role in osteoarthritis.