RESEARCH PROJECTS

Osteoarthritis Pathogenesis and Therapy

Articular cartilage has a unique organization of matrix macromolecules synthesized and maintained by chondrocytes. Large aggregating proteoglycans are highly negatively charged and produce an osmotic swelling pressure that resists compression. This swelling pressure is counter-balanced by the restraining force of a collagen fibrillar network composed primarily of type II and type XI collagens interconnected with type IX collagen. In addition to the major structural molecules, cartilage also contains an abundance of other matrix components including small proteoglycans, adhesion and connecting molecules, and various growth factors. Together, these extracellular matrix components provide the biomechanical properties of articular cartilage necessary for smooth joint movement and the distribution of load.

Osteoarthritis is characterized by a progressive degeneration of articular cartilage and increasingly compromised joint function. While initiating events are variable and can include developmental and/or acquired components, disease progression involves many common pathways. Cartilage matrix components are broken down and the normal balance between their synthesis and degradation is lost. Over time, the structural integrity of articular cartilage fails and joint movement becomes increasingly painful and restricted. Our research is focused on how chondrocyte function changes during the development and progression of osteoarthritis.

• How do chondrocytes contribute to the pathogenesis of this disease?

• What limits their ability to maintain the structural integrity of cartilage matrix?

• How do therapeutic strategies used in patients suffering from osteoarthritis impact chondrocyte function?

Osteoarthritic cartilage illustrating a loss of structural integrity on the joint surface.