Intra-articular hyaluronan (hyaluronic acid) and hylans for the treatment of osteoarthritis: mechanisms of action

Abstract

Although the predominant mechanism of intra-articular hyaluronan (hyaluronic acid) (HA) and hylans for the treatment of pain associated with knee osteoarthritis (OA) is unknown, in vivo, in vitro, and clinical studies demonstrate various physiological effects of exogenous HA. HA can reduce nerve impulses and nerve sensitivity associated with the pain of OA. In experimental OA, this glycosaminoglycan has protective effects on cartilage, which may be mediated by its molecular and cellular effects observed in vitro. Exogenous HA enhances chondrocyte HA and proteoglycan synthesis, reduces the production and activity of proinflammatory mediators and matrix metalloproteinases, and alters the behavior of immune cells. Many of the physiological effects of exogenous HA may be a function of its molecular weight. Several physiological effects probably contribute to the mechanisms by which HA and hylans exert their clinical effects in knee OA.

Figure 1

Several factors contribute to the breakdown and synthesis of cartilage. In osteoarthritis (OA), the balance between cartilage degradation and synthesis leans toward degradation. BMP, bone morphogenetic protein; bFGF, basic fibroblastic growth factor; IGF, insulin-like growth factor; IL, interleukin; MMP, matrix metalloproteinase; PG, proteoglycan; TGF, transforming growth factor; TIMP, tissue inhibitor of metalloproteinases; TNF, tumor necrosis factor.

Figure 2

The extracellular matrix of cartilage is composed of proteoglycans attached to a backbone of hyaluronic acid that is intertwined among collagen fibrils. Proteoglycans have both chondroitin-sulfate- and keratin-sulfate-rich regions, and link proteins facilitate binding of aggrecan to hyaluronic acid.