Anion Channels in Osteoarthritic Chondrocytes

Abstract

Osteoarthritis (OA) is the most common form of arthritis and represents a global health problem. OA is estimated to affect 40% of the population over 70 years of age and is a major cause of pain and physical disability (Lawrence, 2008). This is a condition that predominantly involves hip, knee, spine, foot and hands. Several risk factors have been associated with the initiation and progression of OA, increasing age, sex, obesity, occupational loading, malalignment, articular trauma and crystal deposition. OA is a chronic degenerative joint disorder characterized primarily by destruction of articular cartilage, formation of reparative fibrocartilage and subchondral bone remodelling. However, not only the cartilage and bone are affected, also the synovium and the jointstabilizing structures such as ligaments and meniscus (Baker‐LePain, 2010). Apparently, all the tissues of the joint respond to mechanical stress with the consequent loss of function and clinical deterioration. The application of mechanical forces under physiological conditions is a preponderant factor in cartilage homeostasis. It is now well know, that environmental factors, such as compressive and tensile forces, load and shear stress have a significant influence on the chondrocyte metabolism. Also, conditions that alter the load distribution on the articular surface can induce the development of OA (Roos, 2005). This degradative process of the cartilage in OA is a consequence of an imbalance between anabolism and catabolism of chondrocytes. Generally, chondrocytes respond with increased expression of inflammatory mediators and matrix-degrading proteinases (Kurz, 2005). Other effect observed in chondrocytes under mechanical stimulation is the change in membrane and osmotic potential (Wright, 1992, Bush, 2001). In OA, chondrocytes undergo depolarization instead of hyperpolarization (Millward-Sadler, 2000), and the decrease of the osmotic potential has been associated with loss of volume control in early stages of OA (Stockwell, 1991, Bush, 2003). However, the sequence of mechanobiological events necessary for the maintenance of extracellular matrix (ECM) homeostasis and its involvement in the pathogenesis of OA is still poorly understood.