![]() ![]() HA (a polymer of disaccharides) can be 25,000 disaccharide repeats in length with a MW of 5,000–20,000,000 Da. Within the joint cavity, HA molecules are predominately synthesized by type B synoviocytes. HA also occurs within cells and it has been reported to have roles inside the cell ( 37, 39). HA is an important constituent of ECM and contributes to cell proliferation, migration, and morphogenesis ( 10, 36– 38). The greatest amount of HA is present in the skin (about half of the total HA ( 32), synovial fluid ( 33), the vitreous body ( 34), and the umbilical cord ( 35). Out of 15 g total HA, 5 g turns over daily ( 31). Structural formula of hyaluronic acid (HA).Ī person with an average weight of 70 kg has about 15 g of HA, which is present in joints, skin, eyes and other organs and tissues (connective, epithelial, and neural) of the body ( 7, 29, 30). This review describes physico-chemical and rheological properties, cellular and molecular mechanisms in pharmacological and therapeutic effects in health and disease conditions, and toxicity and safety considerations of HA. In humans, HA has been used since the 1970s for treating joint pain and other health conditions ( 8, 10, 16– 22). HA has recently become more widely accepted in the armamentarium of therapies for OA pain ( 14, 15). HA is reported to be a unique biomolecule because its biological functions can be attributed to its physico-chemical properties and to its specific interactions with cells and ECM ( 7, 10, 13). Currently, elastoviscous HA solutions and its derivatives (such as Hylans) are commonly used in animals for treatment of arthritic pain. This treatment proved effective and since then it has been widely used in veterinary medicine ( 11, 12). The first therapeutic injections of HA in animal joints were performed on track horses for traumatic arthritis. HA is a major component of the extracellular matrix (ECM) and is normally present in mammalian bone marrow, articular cartilage, and synovial fluid. Most cells in the body have the capability to synthesize HA during some point of their cell cycles, implicating its function in several fundamental biological processes ( 7– 10). In both vertebrates and bacteria, its chemical structure is identical ( 5, 6). Hyaluronic acid (HA) is also produced via microbial ( Streptococcus zooepidemicus, Escherichia coli, Bacillus subtilis, and others) fermentation ( 1– 3), and its molecular weight (MW) is reported to be controlled by UDP-N-acetylglucosamine concentration ( 4). Subsequently, it was found in other organs (joints, skin, rooster comb, human umbilical cord, etc.) and tissues (connective, epithelial, and nervous). The term “hyaluronan” was introduced in 1986 to conform to polysaccharide nomenclature. ![]() In 1934, Karl Meyer and John Palmer isolated for the first time a glycosaminoglycan (GAG) from the vitreous humor of the bovine eye and named it “hyaluronic acid” (derived from hyaloid and uronic acid). This review provides a mechanism-based rationale for the use of HA in some disease conditions with special reference to OA. The MW of HA appears to play a critical role in the formulation of the products used in the treatment of diseases. HA is also used in the treatment of ophthalmic, dermal, burns, wound repair, and other health conditions. HA produces anti-arthritic effects via multiple mechanisms involving receptors, enzymes and other metabolic pathways. For that reason, HA has been used for more than four decades in the treatment of OA in dogs, horses and humans. The concentration of HA and its molecular weight (MW) decline as osteoarthritis (OA) progresses with aging. HA has an important role in the biomechanics of normal SF, where it is partially responsible for lubrication and viscoelasticity of the SF. HA is a non-sulfated, naturally occurring non-protein glycosaminoglycan (GAG), with distinct physico-chemical properties, produced by synoviocytes, fibroblasts, and chondrocytes. Hyaluronic acid (HA) content varies widely in different joints and species. Hyaluronic acid (also known as hyaluronan or hyaluronate) is naturally found in many tissues and fluids, but more abundantly in articular cartilage and synovial fluid (SF). ![]()
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