Mechanisms of Beneficial Effects of High Molecular Weight Hyaluronan on Cultured Cartilage Tissue

The efficacy of high molecular weight hyaluronan (HA) in reversing cartilage damage in patients with joint degeneration has not yet been clearly demonstrated, although there is compelling evidence of reduction in parameters of pain. The rationales as to why HA may be beneficial to cartilage structure are diverse and are largely based on studies of in vitro models of cartilage damage. However, there are few studies in these models showing a linkage between effects of HA on cartilage metabolism to an outcome more closely related to osteoarthritis, such as cartilage matrix degradation. Thus, while HA may have a myriad of effects on chondrocytes, perhaps not all of these explain its potential chondroprotective activity. This review discusses selected studies and question whether there is a common explanation for efficacy of HA. It is concluded and proposed that HA may be a weak catabolic mediator that stimulates anabolic processes in cartilage. Thus, the efficacy of HA may be explained by the linkage of catabolic events to subsequent anabolic reparative responses, a newer theme supported by numerous studies.