[[Image:Hyaluronan.png|thumb|right|The repeating disaccharide unit of hyaluronan]]
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==Overview==
|fdaLIADAdult======Condition1=====
'''Hyaluronan''' (also called '''hyaluronic acid''' or '''hyaluronate''') is a non-sulfated [[glycosaminoglycan]] distributed widely throughout [[connective tissue|connective]], [[epithelial tissue|epithelial]], and [[neural tissue]]s. 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 [[tumor]]s. 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.<ref>{{cite journal|author=Stern R | title=Hyaluronan catabolism: a new metabolic pathway | journal=Eur J Cell Biol|volume=83 | issue=7 | pages=317-25 | month=August | year=2004 | pmid = 15503855 | accessdate=2007-06-12}}</ref>
== Functions ==
* Dosing Information
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.
:* Dosage
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.<ref>Holmes et al. (1988) Hyaluronic acid in human articular cartilage. Age-related changes in content and size. Biochem J 250:435-441.</ref>
=====Condition2=====
Hyaluronan is also a major component of [[skin]], where it is involved in tissue repair. When [[skin]] is excessively exposed to [[UVB radiation|UVB rays]], it becomes inflamed ([[sunburn]]) and the [[Cell (biology)|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.<ref>Averbeck M et al. (2007) Differential regulation of hyaluronan metabolism in the epidermal and dermal compartments of human skin by UVB irradiation. J Invest Dermatol 127:687-697.</ref>
* Dosing Information
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.
:* Dosage
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]].
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== Structure ==
* Dosing Information
The [[chemical structure]] of hyaluronan was determined in the [[1950s]] in the laboratory of [[Karl Meyer (biochemist)|Karl Meyer]]. Hyaluronan is a polymer of [[disaccharide]]s themselves, composed of [[D-glucuronic acid]] and [[D-N-acetylglucosamine]], linked together via alternating β-1,4 and β-1,3 [[glycosidic bond]]s. Hyaluronan can be 25,000 disaccharide repeats in length. Polymers of hyaluronan can range in size from 5,000 to 20,000,000 [[Atomic_mass_unit|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.<ref>Saari H et al. (1993) Differential effects of reactive oxygen species on native synovial fluid and purified human umbilical cord hyaluronate. Inflammation 17:403-415.</ref>
:* Dosage
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.
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== Synthesis ==
* Dosing Information
Hyaluronan is synthesized by a class of [[integral membrane protein]]s called [[hyaluronan synthase]]s, 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.
:* Dosage
Hyaluronan synthesis (HAS) has been shown to be inhibited by 4-Methylumbelliferone (hymecromone, heparvit), a 7-Hydroxy-4-methylcoumarin derivative.<ref>Kakizaki, I., Kojima, K., Takagaki, K., Endo, M., Kannagi, R., Ito, M., Maruo, Y., Sato, H., Yasuda, T., Mita, S., Kimata, K. and Itano, N. (2004) A novel mechanism for the inhibition of hyaluronan biosynthesis by 4-methylumbelliferone. J. Biol. Chem. 279, 33281–33289.</ref> This selective inhibition (without inhibiting other [[Glycosaminoglycans]]) may prove useful in preventing [[metastasis]] of malignant tumor cells.<ref>Yoshihara S, Kon A, Kudo D, Nakazawa H, Kakizaki I, Sasaki M, Endo M, Takagaki K., A hyaluronan synthase suppressor, 4-methylumbelliferone, inhibits liver metastasis of melanoma cells. FEBS Lett 2005;579:2722–6. PMID: 15862315</ref>
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== Degradation ==
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Hyaluronan is degraded by a family of enzymes called [[hyaluronidase]]s. 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.
* Developed by:
== Medical applications ==
* Class of Recommendation:
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.<ref>http://www.alconlabs.com/us/aj/products/Surgical_Cataract/A251_Viscoelastics.jhtml</ref><ref>http://www.bausch.com.br/br/resource/surgical/cataract/amviscstatement.jsp</ref>
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Hyaluronan is also used to treat [[osteoarthritis]] of the knee.<ref>{{cite journal | author=Puhl W | coauthors=Scharf P | title=Intra-articular hyaluronan treatment for osteoarthritis | journal=
Ann Rheum Dis | volume=56 | issue=7 | pages=637-40 | year=1997 | month=July | pmid = 9486013 | accessdate=2007-06-13}}</ref> 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 [[chondrocyte|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.<ref>http://www.attract.wales.nhs.uk/question_answers.cfm?question_id=1889</ref><ref>http://rheumatology.oxfordjournals.org/cgi/content/full/41/11/1240</ref> 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.<ref>http://www.biochem.northwestern.edu/ibis/articles/Shea/Segura_et_al_Biomat_2004.pdf</ref><ref>http://www.biomateria.com/bio_skin_3.htm</ref>
* Dosing Information
In some cancers, hyaluronan levels correlate well with malignancy and poor prognosis. Hyaluronan is thus often used as a [[tumor marker]] for [[prostate cancer|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 [[leukocyte|white blood cells]], which mediate the [[immune response]].
:* Dosage
In 2007, the [[European Medicines Agency|EMEA]] extended its approval of Hylan GF-20 as a treatment for ankle and shoulder osteoarthritis pain.<ref>{{cite web|url=http://www.library.nhs.uk/musculoskeletal/ViewResource.aspx?resID=182567 |title=Hylan G-F 20 (Synvisc) approved by EMEA for pain due to ankle and shoulder OA |accessdate=2007-07-09 |publisher=[[National Health Service]]}}</ref>
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== Cosmetic applications ==
There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
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]].<ref>{{cite web | first= | last= | coauthors= | title=New Device Approval | date=2003-12-12 | publisher=[[U.S. Food and Drug Administration]] | url =http://www.fda.gov/cdrh/MDA/DOCS/p020023.html | work = | pages = | accessdate = 2007-08-17 | language = }}</ref>
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== Etymology ==
* Dosing Information
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.
:* Dosage
The term ''hyaluronate'' refers to the [[conjugate acid|conjugate base]] of hyaluronic acid. Because the molecule typically exists ''in vivo'' in its polyanionic form, it is most commonly referred to as ''hyaluronan''.
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==References==
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== External links ==
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* {{MeshName|Hyaluronan}}
{{Glycosaminoglycans}}
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{{Preparations for treatment of wounds and ulcers}}
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[[Category:Glycosaminoglycans]]
[[de:Hyaluronsäure]]
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[[fr:Acide hyaluronique]]
[[it:Acido ialuronico]]
[[nl:Hyaluronan]]
[[ja:ヒアルロン酸]]
[[pl:Kwas hialuronowy]]
[[sk:Kyselina hyalurónová]]
[[zh:玻尿酸]]
[[ru:Гиалуроновая кислота]]
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Overview
Hyaluronic acid (topical) is a {{{drugClass}}} that is FDA approved for the {{{indicationType}}} of {{{indication}}}. There is a Black Box Warning for this drug as shown here. Common adverse reactions include .
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