New aspects of the pathogenesis of osteoarthritis: the role of fibroblast-like chondrocytes in late stages of the disease.

Abstract

It is thought that the general increase in life expectancy will make osteoarthritis the fourth leading cause of disability by the year 2020. Even though the pathogenesis of idiopathic osteoarthritis has not been fully elucidated, the main features of the disease process are the altered interactions between the chondrocytes and their surrounding extracellular matrix. In the course of these disturbances, three types of chondrocytes are typically present in the pathologically altered extracellular matrix of the articular cartilage: healthy chondrocytes which are continually undergoing degeneration, degenerated cells which are continually being degraded and finally fibroblast-like chondrocytes which seem not to be influenced by this process and, therefore, are found in ever-increasing numbers. These fibroblast-like chondrocytes take part in tissue regeneration even in advanced stages of osteoarthritis, but only in as much as they form fibrocartilaginous or scar tissue, since, as we were able to show, they mainly synthesize collagen type I and not collagen type II, typical for healthy cartilage. However, we were further able to show that fibroblast-like chondrocytes also produce increasing amounts of the proteoglycans decorin and biglycan which physiologically are involved in the formation of collagen type II, as well as perlecan. These multifunctional fibroblast-like chondrocytes could present an ideal therapeutic starting point if they could be modified to synthesize the collagen type II typical for cartilage and to, thereby, contribute to reversing the damage of the joint cartilage that has occurred by the late stages of osteoarthritis.