Hyaluronan and related glycosaminoglycans (HA and GAGs) (HA and GAGs)

Hyaluronan (HA) and related glycosaminoglycans (GAGs) are high-molecular-weight linear polysaccharides that constitute a major part of the extracellular matrix in vertebrate tissues [1]. HA is unique among GAGs because it is non-sulfated, can reach enormous molecular sizes, and is synthesized by hyaluronan synthases at the inner surface of the plasma membrane rather than in the Golgi apparatus [2]. These molecules are essential for maintaining tissue hydration and osmotic balance, while also serving as a scaffold for other matrix components and interacting with cell-surface receptors like CD44 to regulate cell proliferation and migration [3]. In clinical contexts, HA accumulation is a hallmark of many solid tumors, where it increases interstitial fluid pressure and creates a physical barrier to drug delivery [4]. Conversely, the loss of HA and other GAGs in articular cartilage is a primary driver of osteoarthritis progression. Therapeutic interventions include the use of hyaluronidases to degrade HA for enhanced drug penetration and the administration of exogenous HA for viscosupplementation in joints [5].

Other names

Hyaluronic acidHyaluronateMucopolysaccharidesAcidic glycosaminoglycansExtracellular matrix polysaccharides

Enzymatic degradation of hyaluronan to increase tissue permeability and reduce interstitial pressure; inhibition of hyaluronan synthase to decrease polymer production; supplementation of exogenous glycosaminoglycans to restore joint lubrication and viscoelasticity.