Hyaluronic Acid; Uses, Dosage, Side Effects, Interactions

Hyaluronic Acid; Uses, Dosage, Side Effects, Interactions

Hyaluronic Acid is a glucosaminoglycan consisting of the D-glucuronic acid and N-acetyl-D-glucosamine disaccharide units that is a component of connective tissue, skin, vitreous humor, umbilical cord, synovial fluid and the capsule of certain microorganisms contributing to adhesion, elasticity, and viscosity of extracellular substances

Hyaluronic acid also called hyaluronan, is an anionic, nonsulfated glycosaminoglycan distributed widely throughout connective, epithelial, and neural tissues. It is unique among glycosaminoglycans in that it is nonsulfated, forms in the plasma membrane instead of the Golgi apparatus, and can be very large, with its molecular weight often reaching the millions.One of the chief components of the extracellular matrix, hyaluronan contributes significantly to cell proliferation and migration, and may also be involved in the progression of some malignant tumors

Mechanism of Action of Hyaluronic Acid 

Osteoarthritis (OA), the most common type of arthritis, is a degenerative joint disease. Oxidative stress is well known to play important roles in cartilage degradation and pathogenesis of OA. The intra-articular injection of hyaluronic acid (IAHA) is accepted as an effective clinical therapy for OA, but we do not yet fully understand the mechanisms underlying the effects of HA on OA chondrocytes under oxidative stress. Here, we show for the first time that IAHA significantly reduces the synovial fluid levels of hydrogen peroxide (H2O2) and superoxide (O2(-)) in patients with knee OA. We also demonstrate that HA suppresses H2O2-induced cell death in human OA chondrocytes. Proteomic approaches (2-DE combined with mass spectrometry) allowed us to identify 13 protein spots corresponding to 12 non-redundant proteins as HA-regulated proteins in OA chondrocytes under oxidative stress. The expression levels of three putative HA-regulated proteins (TALDO, ANXA1, and EF2) in control, H2O2-, HA- and HA/H2O2-treated OA chondrocytes were verified by Western blotting and the results indeed support the notion that HA acts in anti-oxidation, anti-apoptosis, and the promotion of cell survival. Our results collectively demonstrate the utility of proteomic approaches and provide new insights into the chondroprotective effects of HA on OA. In the present study, we show for the first time that IAHA reduces the levels of H2O2 and O2(-) in synovial fluids from OA patients. We used primary cultured human OA chondrocytes as a model, treated cells with H2O2 to partly mimic their physiological conditions under oxidative stress, and examined the protective effects of HA. The proteomic approach allowed us to identify candidate proteins regulated by H2O2 and/or HA in OA chondrocytes. We found that proteins functioning in stress responses, apoptosis and protein synthesis were consistently regulated by HA in chondrocytes under oxidative stress. These novel results contribute to our understanding of the molecular mechanisms underlying HA-mediated chondroprotection.

ICAM-1 is known mainly as a metabolic cell surface receptor for hyaluronic acid, and this protein may be responsible mainly for the clearance of hyaluronic acid from lymph and blood plasma, which accounts for perhaps most of its whole-body turnover. Ligand binding of this receptor, thus, triggers a highly coordinated cascade of events that includes the formation of an endocytotic vesicle, its fusion with primary lysosomes, enzymatic digestion to monosaccharides, active transmembrane transport of these sugars to cell sap, phosphorylation of GlcNAc and enzymatic deacetylation. ICAM-1 may also serve as a cell adhesion molecule, and the binding of hyaluronic acid to ICAM-1 may contribute to the control of ICAM-1-mediated inflammatory activation.

Indications of Hyaluronic Acid 

  • Hyaluronic acid has been used in attempts to treat osteoarthritis of the knee via injecting it into the joint. It has not been proven, however, to generate significant benefit and has potentially severe adverse effects.
  • Dry, scaly skin such as that caused by atopic dermatitis may be treated with skin lotion containing sodium hyaluronate as its active ingredient.
  • Hyaluronic acid has been used in various formulations to create artificial tears to treat dry eye.
  • Used to treat knee pain in patients with joint inflammation (osteoarthritis). It is usually used in patients who have not responded to other treatments such as acetaminophen, exercise, or physical therapy.
  • Hyaluronic acid may also be used in plastic surgery to reduce wrinkles on the face or as a filler in other parts of the body. May be used in ophthalmology to assist in the extraction of cataracts, the implantation of intraocular lenses, corneal transplants, glaucoma filtration, retinal attachment and in the treatment of dry eyes. Finally, hyaluronic acid is also used to coat the bladder lining in treating interstitial cystitis.

Therapeutic Indication of Hyaluronic Acid



Hyaluronic Acid


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