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

Arthritis Res Ther. 2003;5(2):54-67. doi: 10.1186/ar623. Epub 2003 Jan 14.


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.

Publication types

  • Review

MeSH terms

  • Cartilage / drug effects
  • Extracellular Matrix / metabolism
  • Humans
  • Hyaluronic Acid / administration & dosage
  • Hyaluronic Acid / analogs & derivatives
  • Hyaluronic Acid / physiology
  • Hyaluronic Acid / therapeutic use*
  • Inflammation / drug therapy
  • Inflammation Mediators / metabolism
  • Injections, Intra-Articular
  • Leukocytes / drug effects
  • Leukocytes / immunology
  • Osteoarthritis / drug therapy*
  • Osteoarthritis / etiology
  • Pain / drug therapy
  • Synovial Fluid / chemistry
  • Synovial Fluid / metabolism


  • Inflammation Mediators
  • hylan
  • Hyaluronic Acid