Information about Hyaluronic Acid

Hyaluronan (also called hyaluronic acid or hyaluronate) is a non-sulfated glycosaminoglycan distributed widely throughout connective, epithelial, and neural tissues. It is one of the chief components of the extracellular matrix, contributes significantly to cell proliferation and migration, and may also be involved in the progression of some malignant tumors. The average 70-kg man has roughly 15 grams of hyaluronan in his body, one-third of which is turned over (degraded and synthesised) every day.^[1]

Functions

Until the late 1970s, hyaluronan was described as a "goo" molecule, a ubiquitous carbohydrate polymer that is part of the extracellular matrix. For example, hyaluronan is a major component of the synovial fluid and was found to increase the viscosity of the fluid. Along with lubricin, it is one of the fluid's main lubricating components.

Hyaluronan is an important component of articular cartilage, where it is present as a coat around each cell (chondrocyte). When aggrecan monomers bind to hyaluronan in the presence of link protein, large highly negatively-charged aggregates form. These aggregates imbibe water and are responsible for the resilience of cartilage (its resistance to compression). The molecular weight (size) of hyaluronan in cartilage decreases with age, but the amount increases.^[2]

Hyaluronan is also a major component of skin, where it is involved in tissue repair. When skin is excessively exposed to UVB rays, it becomes inflamed (sunburn) and the cells in the dermis stop producing as much hyaluronan, and increase the rate of its degradation. Hyaluronan degradation products also accumulate in the skin after UV exposure.^[3]

While it is abundant in extracellular matrices, hyaluronan also contributes to tissue hydrodynamics, movement and proliferation of cells, and participates in a number of cell surface receptor interactions, notably those including its primary receptor, CD44. Upregulation of CD44 itself is widely accepted as a marker of cell activation in lymphocytes. Hyaluronan's contribution to tumor growth may be due to its interaction with CD44. Receptor CD44 participates in cell adhesion interactions required by tumor cells.

Although hyaluronan binds to receptor CD44, there is evidence that hyaluronan degradation products transduce their inflammatory signal through Toll-like receptor 2 (TLR2), TLR4 or both TLR2, and TLR4 in macrophages and dendritic cells. TLR and hyaluronan play a role in innate immunity.

Structure

The chemical structure of hyaluronan was determined in the 1950s in the laboratory of Karl Meyer. Hyaluronan is a polymer of disaccharides themselves, composed of D-glucuronic acid and D-N-acetylglucosamine, linked together via alternating β-1,4 and β-1,3 glycosidic bonds. Hyaluronan can be 25,000 disaccharide repeats in length. Polymers of hyaluronan can range in size from 5,000 to 20,000,000 Da in vivo. The average molecular weight in human synovial fluid is 3−4 million Da, and hyaluronan purified from human umbilical cord is 3,140,000 Da.^[4]

Hyaluronan is energetically stable in part because of the stereochemistry of its component disaccharides. Bulky groups on each sugar molecule are in sterically favored positions, whereas the smaller hydrogens assume the less-favorable axial positions.

Synthesis

Hyaluronan is synthesized by a class of integral membrane proteins called hyaluronan synthases, of which vertebrates have three types: HAS1, HAS2, and HAS3. These enzymes lengthen hyaluronan by repeatedly adding glucuronic acid and N-acetylglucosamine to the nascent polysaccharide as it is extruded through the cell membrane into the extracellular space.

Hyaluronan synthesis (HAS) has been shown to be inhibited by 4-Methylumbelliferone (hymecromone, heparvit), a 7-Hydroxy-4-methylcoumarin derivative.^[5] This selective inhibition (without inhibiting other Glycosaminoglycans) may prove useful in preventing metastasis of malignant tumor cells.^[6]

Degradation

Hyaluronan is degraded by a family of enzymes called hyaluronidases. In humans, there are at least seven types of hyaluronidase-like enzymes, several of which are tumor suppressors. The degradation products of hyaluronan, the oligosaccharides and very low-molecular-weight hyaluronan, exhibit pro-angiogenic properties. In addition, recent studies showed that hyaluronan fragments, not the native high-molecular mass of hyaluronan, can induce inflammatory responses in macrophages and dendritic cells in tissue injury and in skin transplant rejection.

Medical applications

Hyaluronan is naturally found in many tissues of the body, such as skin, cartilage, and the vitreous humor. It is therefore well suited to biomedical applications targeting these tissues. The first hyaluronan biomedical product, Healon, was developed in the 1970s and 1980s, and is approved for use in eye surgery (i.e., corneal transplantation, cataract surgery, glaucoma surgery and surgery to repair retinal detachment). Other biomedical companies also produce brands of hyaluronan for ophthalmic surgery.^[7][8]

Hyaluronan is also used to treat osteoarthritis of the knee.^[9] Such treatments, called viscosupplementation'', are administered as a course of injections into the knee joint and are believed to supplement the viscosity of the joint fluid, thereby lubricating the joint, cushioning the joint, and producing an analgesic effect. It has also been suggested that hyaluronan has positive biochemical effects on cartilage cells. However, some placebo controlled studies have cast doubt on the efficacy of hyaluronan injections, and hyaluronan is recommended primarily as a last alternative to surgery.^[10][11] Oral use of hyaluronan has been lately suggested, although its effectiveness needs to be demonstrated. At present, there are some preliminary clinical studies that suggest that oral administration of Hyaluronan has a positive effect on osteoarthritis.

Due to its high biocompatibility and its common presence in the extracellular matrix of tissues, hyaluronan is gaining popularity as a biomaterial scaffold in tissue engineering research.^[12][13]

In some cancers, hyaluronan levels correlate well with malignancy and poor prognosis. Hyaluronan is thus often used as a tumor marker for prostate and breast cancer. It may also be used to monitor the progression of the disease.

Hyaluronan may also be used postoperatively to induce tissue healing, notably after cataract surgery. Current models of wound healing propose that larger polymers of hyaluronic acid appear in the early stages of healing to physically make room for white blood cells, which mediate the immune response.

In 2007, the EMEA extended its approval of Hylan GF-20 as a treatment for ankle and shoulder osteoarthritis pain.^[14]

Cosmetic applications

Hyaluronan is a common ingredient in skin care products.

In 2003 the FDA approved hyaluronan injections for filling soft tissue defects under the trade name Restylane.^[15]

Etymology

Hyaluronic acid is derived from hyalos (Greek for vitreous) and uronic acid because it was first isolated from the vitreous humor and possesses a high uronic acid content.

The term hyaluronate refers to the conjugate base of hyaluronic acid. Because the molecule typically exists in vivo in its polyanionic form, it is most commonly referred to as hyaluronan.

References

External links

• MeSH Hyaluronan

•  • [ e] Polysaccharides: glycosaminoglycans
Chondroitin sulfate - Dermatan sulfate - Heparin - Heparan sulfate - Hyaluronan - Keratan sulfate

•  • [ e] Preparations for treatment of wounds and ulcers (D03)
Cicatrizants	Cadexomer iodine - Dextranomer - Dexpanthenol - Calcium pantothenate - Hyaluronic acid - Becaplermin - Glyceryl trinitrate - Isosorbide dinitrate - Crilanomer - Enoxolone
Proteolytic enzymes	Trypsin - Clostridiopeptidase

Glycosaminoglycans (GAGs) or mucopolysaccharides are long unbranched polysaccharides consisting of a repeating disaccharide unit.

Production

Protein cores made in the rough endoplasmic reticulum are posttranslationally modified by glycosyltransferases in the Golgi
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Connective tissue is one of the four types of tissue in traditional classifications (the others being epithelial, muscle, and nervous tissue.) It is largely a category of exclusion rather than one with a precise definition, but all or most tissues in this category are similarly:
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epithelium is a tissue composed of a layer of cells. Epithelium lines both the outside (skin) and the inside cavities and lumen of bodies. The outermost layer of our skin is composed of dead stratified squamous, keratinized epithelial cells.
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Nervous tissue is the fourth major class of vertebrate tissue. The function of the nervous tissue is in communication between parts of the body. It is composed of neurons, which transmit impulses, and the neuroglia, which assist propagation of the nerve impulse as well as provide
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For malignant tumors specifically, see .

Tumor or tumour (via Old French tumour from Latin tumor "swelling") is an abnormal growth or mass of tissue. A tumor can be either malignant or benign.
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Centuries: 19th century - 20th century - 21st century

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1975 1976 1977 1978 1979

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- The 1970s decade refers to the years from 1970 to 1979, also called
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Synovial fluid is a thick, stringy fluid found in the cavities of synovial joints. With its egg-like consistency (synovial comes from Latin for "egg"), synovial fluid reduces friction between the articular cartilage and other tissues in joints to lubricate and cushion them
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Lubricin is a large, water soluble glycoprotein encoded by the PRG4 gene. It has a molecular weight of 206,000 Daltons and consists of approximately equal proportions of protein and glycosaminoglycans.
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Cartilage is a type of dense connective tissue. It is composed of collagen fibers and/or elastin fibers, and can supply smooth surfaces for the movement of articulating bones.
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Chondrocytes (from Greek chondros cartilage + kytos cell) are the only cells found in cartilage. They produce and maintain the cartilaginous matrix, which consists mainly of collagen and proteoglycans.
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Aggrecan, or large aggregating proteoglycan, is a proteoglycan, or a protein modified with carbohydrates; the human form of the protein is 2316 amino acids long and can be expressed in multiple isoforms due to alternative splicing.
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For the band, see Resilience (band).

Resilience generally means the ability to recover from (or to resist being affected by) some shock, insult, or disturbance. However, it is used quite differently in different fields.
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Cartilage is a type of dense connective tissue. It is composed of collagen fibers and/or elastin fibers, and can supply smooth surfaces for the movement of articulating bones.
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molecular mass (abbreviated Mr) of a substance, formerly also called molecular weight and abbreviated as MW, is the mass of one molecule of that substance, relative to the unified atomic mass unit u (equal to 1/12 the mass of one atom of carbon-12).
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Cartilage is a type of dense connective tissue. It is composed of collagen fibers and/or elastin fibers, and can supply smooth surfaces for the movement of articulating bones.
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Skin layers: epidermis, dermis, and subcutis, showing a hair follicle, sweat gland & sebaceous gland.]] In zootomy and dermatology, skin is the largest organ of the integumentary system made up of multiple layers of epithelial tissues that guard underlying muscles and organs.
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Skin layers: epidermis, dermis, and subcutis, showing a hair follicle, sweat gland & sebaceous gland.]] In zootomy and dermatology, skin is the largest organ of the integumentary system made up of multiple layers of epithelial tissues that guard underlying muscles and organs.
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Ultraviolet (UV) light is electromagnetic radiation with a wavelength shorter than that of visible light, but longer than soft X-rays. It is so named because the spectrum starts with wavelengths slightly shorter than the wavelengths humans identify as the color violet
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For other uses, see Sunburn (disambiguation).

SunBurn is an annual regional event held in Florida. Radical self-reliance and self-expression are the goals, and community is emphasized.
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The CD44 protein is a cell-surface glycoprotein involved in cell-cell interactions, cell adhesion and migration. It is a receptor for hyaluronic acid and can also interact with other ligands, such as osteopontin, collagens, and matrix metalloproteinases (MMPs).
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The CD44 protein is a cell-surface glycoprotein involved in cell-cell interactions, cell adhesion and migration. It is a receptor for hyaluronic acid and can also interact with other ligands, such as osteopontin, collagens, and matrix metalloproteinases (MMPs).
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TLR-2 is the name for a biomolecule, which plays a role in the human immune system. It is a membrane protein, a receptor, which sits on the surface of certain cells and which can recognize native or foreign substances, and passes on appropriate signals to the cell and/or the
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Macrophages (Greek: "big eaters", from makros "large" + phagein "eat") are cells within the tissues that originate from specific white blood cells called monocytes.
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Dendritic cells (DCs) are immune cells and form part of the mammalian immune system. Their main function is to process antigen material and present it on the surface to other cells of the immune system, thus functioning as antigen-presenting cells.
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See also:  and

The innate immune system comprises the cells and mechanisms that defend the host from infection by other organisms, in a non-specific manner.
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Chemical structure refers to both molecular geometry and to electronic structure. Molecular geometry refers to the spatial arrangement of atoms in a molecule and the chemical bonds that hold the atoms together.
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worldwide view.

2nd millennium
Centuries: 19th century - 20th century - 21st century

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1955 1956 1957 1958 1959

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A disaccharide is a sugar (a carbohydrate) composed of two monosaccharides.^[1]

'Disaccharide' is one of the four chemical groupings of carbohydrates (monosaccharide, disaccharide, oligosaccharide, and polysaccharide).
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