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Hyaluronic acid also called hyaluronan, is an anionic, nonsulfated glycosaminoglycan distributed widely throughout connective, epithelial, and neural tissues.
Hyaluronic acid is unique among glycosaminoglycans as it is non-sulfated, forms in the plasma membrane instead of the Golgi apparatus, and can be very large: human synovial Hyaluronic acid averages about 7 million Da per molecule, or about 20,000 disaccharide monomers, while other sources mention 3–4 million Da
IUPAC name: (1→4)-(2-Acetamido-2-deoxy-D-gluco)-(1→3)-D-glucuronoglycan
CAS Number: 9004-61-9
EC Number: 232-678-0
Chemical formula: (C14H21NO11)n
Other names: Hyaluronic Acid, 9004-61-9, S270N0TRQY, Synvisc, Hyruan Plus, 232-678-0, CHEBI:16336, Emervel, Hyal-Joint, Hyalo-Oligo, Hyalobarrier gel, Hyalofill, Hyalorigo, Macronan, Mucoitin, Nutra-HAF, Sepracoat, Sepragel Sinus, Sofast, UNII-S270N0TRQY, Viscofill Extra, Acid, Hyaluronic, Captique, DTXSID7046750, EINECS 232-678-0, Gengicure, HSDB 7240, HYALURON 3S SERUM, HYALURONIC ACID (STREPTOCOCCUS EQUI), Hyaluronsaeure, MAXCLINIC HYALURONIC MESO CHANGE ROLLER, MORISU, PRO PH Filler, UNII-B7SG5YV2SI, WELLAGE Hyaluronic Acid Micro Needle, acide hyaluronique, acido hialuronico
The average 70 kg (150 lb) person has roughly 15 grams of hyaluronan in the body, one third of which is turned over (i.e., degraded and synthesized) per day.
As one of the chief components of the extracellular matrix, it contributes significantly to cell proliferation and migration, and is involved in the progression of many malignant tumors.
Hyaluronic acid is also a component of the group A streptococcal extracellular capsule, and is believed to play a role in virulence.
Physiological function
Until the late 1970s, hyaluronic acid was described as a "goo" molecule, a ubiquitous carbohydrate polymer that is part of the extracellular matrix.
For example, hyaluronic acid 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.
Hyaluronic acid 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 HAPLN1 (hyaluronic acid and proteoglycan link protein 1), 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.
A lubricating role of hyaluronan in muscular connective tissues to enhance the sliding between adjacent tissue layers has been suggested.
A particular type of fibroblasts, embedded in dense fascial tissues, has been proposed as being cells specialized for the biosynthesis of the hyaluronan-rich matrix.
Their related activity could be involved in regulating the sliding ability between adjacent muscular connective tissues.
Hyaluronic acid is also a major component of skin, where it is involved in repairing tissue. When skin is exposed to excessive 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 then accumulate in the skin after UV exposure.
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 receptors, CD44 and RHAMM.
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 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.
There are limitations including the in vivo loss of this compound limiting the duration of effect.
Wound repair
As a major component of the extracellular matrix, hyaluronic acid has a key role in tissue regeneration, inflammation response, and angiogenesis, which are phases of wound repair.
As of 2023, however, reviews of its effect on healing for chronic wounds including burns, diabetic foot ulcers or surgical skin repairs show either insufficient evidence or only limited positive clinical research evidence.
There is also some limited evidence to suggest that hyaluronic acid may be beneficial for ulcer healing and may help to a small degree with pain control.
Hyaluronic acid combines with water and swells to form a gel, making it useful in skin treatments as a dermal filler for facial wrinkles; its effect lasts for about 6 to 12 months, and treatment has regulatory approval from the US Food and Drug Administration.
Granulation
Granulation tissue is the perfused, fibrous connective tissue that replaces a fibrin clot in healing wounds.
Hyaluronic acid typically grows from the base of a wound and is able to fill wounds of almost any size it heals.
Hyaluronic acid is abundant in granulation tissue matrix.
A variety of cell functions that are essential for tissue repair may attribute to this hyaluronic acid-rich network.
These functions include facilitation of cell migration into the provisional wound matrix, cell proliferation, and organization of the granulation tissue matrix.
Initiation of inflammation is crucial for the formation of granulation tissue; therefore, the pro-inflammatory role of HA as discussed above also contributes to this stage of wound healing.
Cell migration
Cell migration is essential for the formation of granulation tissue.
The early stage of granulation tissue is dominated by a HA-rich extracellular matrix, which is regarded as a conducive environment for the migration of cells into this temporary wound matrix.
HA provides an open hydrated matrix that facilitates cell migration, whereas, in the latter scenario, directed migration and control of related cell mechanisms are mediated via the specific cell interaction between HA and cell surface HA receptors.
It forms links with several protein kinases associated with cell locomotion, for example, extracellular signal-regulated kinase, focal adhesion kinase, and other non-receptor tyrosine kinases.
During fetal development, the migration path through which neural crest cells migrate is rich in HA. HA is closely associated with the cell migration process in granulation tissue matrix, and studies show that cell movement can be inhibited, at least partially, by HA degradation or blocking HA receptor occupancy.
By providing the dynamic force to the cell, HA synthesis has also been shown to associate with cell migration.
Basically, HA is synthesized at the plasma membrane and released directly into the extracellular environment.
This may contribute to the hydrated microenvironment at sites of synthesis, and is essential for cell migration by facilitating cell detachment.
Skin healing
Hyaluronic acid plays an important role in the normal epidermis.
HA also has crucial functions in the reepithelization process due to several of its properties.
These include being an integral part of the extracellular matrix of basal keratinocytes, which are major constituents of the epidermis; its free-radical scavenging function, and its role in keratinocyte proliferation and migration.
In normal skin, HA is found in relatively high concentrations in the basal layer of the epidermis where proliferating keratinocytes are found.
CD44 is collocated with HA in the basal layer of epidermis where additionally it has been shown to be preferentially expressed on plasma membrane facing the Hyaluronic acid rich matrix pouches.
Maintaining the extracellular space and providing an open, as well as hydrated, structure for the passage of nutrients are the main functions of Hyaluronic acid in epidermis.
A report found HA content increases in the presence of retinoic acid (vitamin A).
The proposed effects of retinoic acid against skin photo-damage and photoaging may be correlated, at least in part, with an increase of skin Hyaluronic acid content, giving rise to increased tissue hydration.
Hyaluronic acid has been suggested that the free-radical scavenging property of Hyaluronic acid contributes to protection against solar radiation, supporting the role of CD44 acting as a Hyaluronic acid receptor in the epidermis.
Epidermal Hyaluronic acid also functions as a manipulator in the process of keratinocyte proliferation, which is essential in normal epidermal function, as well as during reepithelization in tissue repair.
In the wound healing process, Hyaluronic acid is expressed in the wound margin, in the connective tissue matrix, and collocating with CD44 expression in migrating keratinocytes.
Medical uses
Hyaluronic acid has been FDA-approved to treat osteoarthritis of the knee via intra-articular injection.
A 2012 review showed that the quality of studies supporting this use was mostly poor, with a general absence of significant benefits, and that intra-articular injection of hyaluronic acid could possibly cause adverse effects.
A 2020 meta-analysis found that intra-articular injection of high molecular weight hyaluronic acid improved both pain and function in people with knee osteoarthritis.
Hyaluronic acid has been used to treat dry eye.
Hyaluronic acid is a common ingredient in skin care products.
Hyaluronic acid is used as a dermal filler in cosmetic surgery.
Hyaluronic acid is typically injected using either a classic sharp hypodermic needle or a micro-cannula. Some studies have suggested that the use of micro-cannulas can significantly reduce vessel embolisms during injections.
Currently, hyaluronic acid is used as a soft tissue filler due to its bio-compatibility and possible reversibility using hyaluronidase.
Complications include the severing of nerves and microvessels, pain, and bruising.
Some side effects can also appear by way of erythema, itching, and vascular occlusion; vascular occlusion is the most worrisome side effect due to the possibility of skin necrosis, or even blindness in a patient.
In some cases, hyaluronic acid fillers can result in a granulomatous foreign body reaction.
Structure
Hyaluronic acid is a polymer of disaccharides, which are composed of D-glucuronic acid and N-acetyl-D-glucosamine, linked via alternating β-(1→4) and β-(1→3) glycosidic bonds.
Hyaluronic acid can be 25,000 disaccharide repeats in length. Polymers of hyaluronic acid 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 hyaluronic acid purified from human umbilical cord is 3,140,000 Da; other sources mention average molecular weight of 7 million Da for synovial fluid.
Hyaluronic acid also contains silicon, ranging 350–1,900 μg/g depending on location in the organism.
Hyaluronic acid 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.
Hyaluronic acid in aqueous solutions self-associates to form transient clusters in solution.
While it is considered a polyelectrolyte polymer chain, hyaluronic acid does not exhibit the polyelectrolyte peak, suggesting the absence of a characteristic length scale between the hyaluronic acid molecules and the emergence of a fractal clustering, which is due to the strong solvation of these molecules.
Biological synthesis
Hyaluronic acid 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 D-glucuronic acid and N-acetyl-D-glucosamine to the nascent polysaccharide as it is extruded via ABC-transporter through the cell membrane into the extracellular space.
The term fasciacyte was coined to describe fibroblast-like cells that synthesize Hyaluronic acid.
Hyaluronic acid synthesis has been shown to be inhibited by 4-methylumbelliferone (hymecromone), a 7-hydroxy-4-methylcoumarin derivative.
This selective inhibition (without inhibiting other glycosaminoglycans) may prove useful in preventing metastasis of malignant tumor cells.
There is feedback inhibition of hyaluronan synthesis by low-molecular-weight hyaluronan (<500 kDa) at high concentrations, but stimulation by high-molecular-weight hyaluronan (>500 kDa), when tested in cultured human synovial fibroblasts.
Bacillus subtilis recently has been genetically modified to culture a proprietary formula to yield hyaluronans, in a patented process producing human-grade product.
Fasciacyte
A fasciacyte is a type of biological cell that produces hyaluronan-rich extracellular matrix and modulates the gliding of muscle fasciae.
Fasciacytes are fibroblast-like cells found in fasciae.
They are round-shaped with rounder nuclei and have less elongated cellular processes when compared with fibroblasts.
Fasciacytes are clustered along the upper and lower surfaces of a fascial layer.
Fasciacytes produce hyaluronan, which regulates fascial gliding.
Biosynthetic mechanism
Hyaluronic acid is a linear glycosaminoglycan (GAG), an anionic, gel-like, polymer, found in the extracellular matrix of epithelial and connective tissues of vertebrates.
Hyaluronic acid is part of a family of structurally complex, linear, anionic polysaccharides.
The carboxylate groups present in the molecule make it negatively charged, therefore allowing for successful binding to water, and making it valuable to cosmetic and pharmaceutical products.
HA consists of repeating β4-glucuronic acid (GlcUA)-β3-N-acetylglucosamine (GlcNAc) disaccharides, and is synthesized by hyaluronan synthases (HAS), a class of integral membrane proteins that produce the well-defined, uniform chain lengths characteristic to HA.
There are three existing types of HASs in vertebrates: HAS1, HAS2, HAS3; each of these contribute to elongation of the HA polymer.
For an HA capsule to be created, this enzyme must be present because it polymerizes UDP-sugar precursors into Hyaluronic acid.
Hyaluronic acid precursors are synthesized by first phosphorylating glucose by hexokinase, yielding glucose-6-phosphate, which is the main HA precursor.
Then, two routes are taken to synthesize UDP-n-acetylglucosamine and UDP-glucuronic acid which both react to form Hyaluronic acid.
Glucose-6-phosphate gets converted to either fructose-6-phosphate with hasE (phosphoglucoisomerase), or glucose-1-phosphate using pgm (α -phosphoglucomutase), where those both undergo different sets of reactions.
UDP-glucuronic acid and UDP-n-acetylglucosamine get bound together to form HA via hasA (HA synthase).
Synthesis of UDP-glucuronic acid
UDP-glucuronic acid is formed from hasC (UDP-glucose pyrophosphorylase) converting glucose-1-P into UDP-glucose, which then reacts with hasB (UDP-glucose dehydrogenase) to form UDP-glucuronic acid.
Synthesis of N-acetyl glucosamine
The path forward from fructose-6-P utilizes glmS (amidotransferase) to form glucosamine-6-P.
Then, glmM (Mutase) reacts with this product to form glucosamine-1-P. hasD (acetyltransferase) converts this into n-acetylglucosamine-1-P, and finally, hasD (pyrophosphorylase) converts this product into UDP-n-acetylglucosamine.
Final step: Two disaccharides form hyaluronic acid
UDP-glucuronic acid and UDP-n-acetylglucosamine get bound together to form HA via hasA (HA synthase), completing the synthesis.
Degradation
Hyaluronic acid can be 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 hyaluronan fragments, not the native high-molecular weight molecule, can induce inflammatory responses in macrophages and dendritic cells in tissue injury and in skin transplant.
Hyaluronan can also be degraded via non-enzymatic reactions. These include acidic and alkaline hydrolysis, ultrasonic disintegration, thermal decomposition, and degradation by oxidants.
Etymology
Hyaluronic acid is derived from hyalos (Greek for vitreous, meaning ‘glass-like’) and uronic acid because it was first isolated from the vitreous humour and possesses a high uronic acid content.
The term hyaluronate refers to the conjugate base of hyaluronic acid. Since the molecule typically exists in vivo in its polyanionic form, it is most commonly referred to as hyaluronan.
History
Hyaluronic acid was first obtained by Karl Meyer and John Palmer in 1934 from the vitreous body in a cow's eye.
The first hyaluronan biomedical product, Healon, was developed in the 1970s and 1980s by Pharmacia, and 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.
Native hyaluronic acid has a relatively short half-life (shown in rabbits) so various manufacturing techniques have been deployed to extend the length of the chain and stabilise the molecule for its use in medical applications.
The introduction of protein-based cross-links, the introduction of free-radical scavenging molecules such as sorbitol, and minimal stabilisation of the Hyaluronic acid chains through chemical agents such as NASHA (non-animal stabilised hyaluronic acid) are all techniques that have been used to preserve its shelf life.
In the late 1970s, intraocular lens implantation was often followed by severe corneal edema, due to endothelial cell damage during the surgery.
Hyaluronic acid was evident that a viscous, clear, physiologic lubricant to prevent such scraping of the endothelial cells was needed.
The name "hyaluronan" is also used for a salt.
Other animals
Hyaluronan is used in treatment of articular disorders in horses, in particular those in competition or heavy work.
Hyaluronic acid is indicated for carpal and fetlock joint dysfunctions, but not when joint sepsis or fracture are suspected.
Hyaluronic acid is especially used for synovitis associated with equine osteoarthritis.
Hyaluronic acid can be injected directly into an affected joint, or intravenously for less localized disorders.
Hyaluronic acid may cause mild heating of the joint if directly injected, but this does not affect the clinical outcome.
Intra-articularly administered medicine is fully metabolized in less than a week.
According to Canadian regulation, hyaluronan in HY-50 preparation should not be administered to animals to be slaughtered for horse meat.
In Europe, however, the same preparation is not considered to have any such effect, and edibility of the horse meat is not affected.
Research
Due to its high biocompatibility and its common presence in the extracellular matrix of tissues, hyaluronan is used as a biomaterial scaffold in tissue engineering research.
In particular, research groups have found hyaluronan's properties for tissue engineering and regenerative medicine may be improved with cross-linking, producing a hydrogel.
Crosslinking may allow a desired shape, as well as to deliver therapeutic molecules into a host.
Hyaluronan can be crosslinked by attaching thiols (see thiomers)(trade names: Extracel, HyStem), hexadecylamides (trade name: Hymovis), and tyramines (trade name: Corgel).
Hyaluronan can also be crosslinked directly with formaldehyde (trade name: Hylan-A) or with divinylsulfone (trade name: Hylan-B).
Due to its ability to regulate angiogenesis by stimulating endothelial cells to proliferate in vitro, hyaluronan can be used to create hydrogels to study vascular morphogenesis.
Hyaluronic acid is a gooey, slippery substance that your body produces naturally.
Scientists have found hyaluronic acid throughout the body, especially in eyes, joints and skin.
Hyaluronic acid also known as hyaluronan or hyaluronate is a gooey, slippery substance that your body produces naturally.
Scientists have found hyaluronic acid throughout the body, especially in eyes, joints and skin.
Hyaluronic acid is a remarkable substance because of all the benefits and uses it has in your body. Here are just a few of the benefits of hyaluronic acid:
Hyaluronic acid helps things move smoothly. Hyaluronic acid helps your joints work like a well-oiled machine.
Hyaluronic acid prevents pain and injury from bones grinding against each other.
Hyaluronic acid helps keep things hydrated. Hyaluronic acid is very good at retaining water. A quarter-teaspoon of hyaluronic acid holds about one and a half gallons of water.
That’s why hyaluronic acid is often used for treating dry eyes.
Hyaluronic acid also used in moisturizing creams, lotions, ointments and serums.
Hyaluronic acid makes your skin flexible.
Hyaluronic acid helps skin stretch and flex and reduces skin wrinkles and lines.
Hyaluronic acid is also proven to help wounds heal faster and can reduce scarring.
Hyaluronic acid is often produced by fermenting certain types of bacteria. Rooster combs (the red, Mohawk-like growth on top of a rooster’s head and face) are also a common source.
There are many ways you can take hyaluronic acid (either on its own or in combination products). Many are available over-the-counter. Some need a doctor’s prescription. For some, you need to see a trained medical professional.
A few of the different ways (available over-the-counter) that you can take hyaluronic acid include:
By mouth: Hyaluronic acid comes in dietary supplements and pills. There’s even a liquid form that you can mix with water and drink.
Taking hyaluronic acid by mouth can have many benefits. These include reducing arthritis pain, improving skin health and more.
On your skin: Hyaluronic acid products come in various forms that you put on your skin. These include shampoos, lotions, creams, gels, ointments, patches and serums. You can also buy hyaluronic acid powder and mix it with water to create a hyaluronic acid serum you can apply to your skin.
Hyaluronic acid has beneficial properties when used on your skin. It’s especially useful for reducing the appearance of wrinkles and age lines.
Eye drops: A wide variety of eye drops contains hyaluronic acid.
For intimate contact: Hyaluronic acid is a common ingredient in gels, creams or personal lubricants for vaginal dryness or pain, especially for women experiencing menopause.
Hyaluronic acid is also available by prescription in the following forms:
By injection: Hyaluronic acid injections into your joints can relieve pain caused by arthritis. It’s also commonly used with medications given in an IV. Healthcare providers may prescribe it off-label to treat bladder pain (such as pain caused by interstitial cystitis).
Under your skin: Fillers containing hyaluronic acid and collagen (a natural protein also found in your body) are approved for injection under your skin. These fillers help restore natural shape and appearance, such as for treating acne scars or adding volume to lips.
In your nose: Some medications use hyaluronic acid because it helps your body absorb them, especially when taken through your nose.
By inhaler/nebulizer: Hyaluronic acid can treat respiratory (breathing) problems such as asthma or infections.
Remember, only trained and qualified medical professionals should give injections. While experts say hyaluronic acid is safe, improper use — especially when injecting it — can lead to severe complications or even death.
Hyaluronic acid belongs to a type of long, complicated chain-like molecules called polymers.
The chain has plenty of spots on it where other chemical compounds (like water, for example) can latch on.
That’s why a quarter-teaspoon of hyaluronic acid can hold about one and a half gallons of water, making it the best polymer natural or artificial for absorbing water (and a key ingredient in moisturizing products).
Because hyaluronic acid has lots of space for other molecules to latch on, hyaluronic acid is great for transporting other molecules throughout your body.
Hyaluronic acid also has the ability to attach itself to cells, which is why targeted delivery of medications using hyaluronic acid is a major topic of study.
Hyaluronic acid’s chain-like structure also means it can act like a scaffold structure, allowing tissues to grow.
This is a key step in how wounds heal on your body.
Scientists have also found hyaluronic acid in human embryos and are studying what role hyaluronic acid plays in reproduction and development.
Long-term use of hyaluronic acid serum on your skin or in a supplement taken by mouth can improve overall skin health.
Hyaluronic acid is also great for helping improve overall skin flexibility and elasticity (meaning it makes your skin more stretchy and soft).
Hyaluronic Acid (which you might find hiding on the labels of some of your skincare products as HA), is naturally occurring in the human body. The substance works as a magnet for moisture, helping your cells retain as much of it as possible so that your skin feels and appears hydrated, plump and healthy.
Just a single gram of hyaluronic acid has the impressive ability to hold up to six litres of water. Add to that, a super smart ability to regulate that moisture within the cells, so as not to drown them and you've got one genius ingredient.
If your skin isn't already lapping up the benefits of hyaluronic acid, this is why it should be:
If skin is sufficiently hydrated, it feels super soft, plump and pillowy and looks so much more radiant.
When skin is hydrated, lines and wrinkles (even the deeper ones) appear diminished, so Hyaluronic Acid is a great ingredient for those with ageing skin who are desperate to cling on to their youthful perkiness.
Hyaluronic Acid works wonders on everyone. 'Hyaluronic acid works for any skin type even sensitive or breakout prone skin, as well as those with an oily complexion.'
Recent research suggests that hyaluronic acid also has antioxidant properties, which means Hyaluronic Acid can act like a shield against free radicals we aren't in control of, like pollution and other aggressors.
The body naturally produces hyaluronic acid, which helps lubricate our tissues.
Hyaluronic Acid plays a role in skin health, wound healing, bone strength, and many other other bodily systems or functions.
Hyaluronic acid, also known as hyaluronan, is a clear, gooey substance that is naturally produced by your body.
The largest amounts of it are found in your skin, connective tissue, and eyes.
Its main function is to retain water to keep your tissues lubricated and moist.
Hyaluronic acid has a variety of uses. Many people take it as a supplement, but it’s also used in topical serums, eye drops, and injections.
Hyaluronic acid supplements can help your skin look and feel more supple.
Hyaluronic acid is a compound found naturally in the skin, where it binds to water to help retain moisture.
However, the natural aging process and exposure to things like ultraviolet radiation from the sun, tobacco smoke, and pollution can decrease its amounts in the skin.
Taking hyaluronic acid supplements may prevent this decline by giving your body extra amounts to incorporate into the skin.
According to one 2014 study, doses of 120–240 milligrams (mg) per day for at least 1 month have been shown to significantly increase skin moisture and reduce dry skin in adults.
Hydrated skin also reduces the appearance of wrinkles, which may explain why several studies show that supplementing with it can make skin appear smoother.
When applied to the surface of the skin, hyaluronic acid serums can reduce wrinkles, redness, and dermatitis.
Some dermatologists even inject hyaluronic acid fillers to keep skin looking firm and youthful
Hyaluronic acid also plays a key role in wound healing.
Hyaluronic acid naturally present in the skin, but its concentrations increase when there is damage in need of repair.
Hyaluronic acid helps wounds heal faster by regulating inflammation levels and signaling the body to build more blood vessels in the damaged area.
In some older studies, applying it to skin wounds has been shown to reduce the size of wounds and decrease pain faster than a placebo or no treatment at all.
Hyaluronic acid also has antibacterial properties, so it may help reduce the risk of infection when applied directly to open wounds.
What’s more, it’s effective at reducing gum disease, speeding up healing after tooth surgery, and eliminating ulcers when used topically in the mouth.
While the research on hyaluronic acid serums and gels is promising, there has been no research to determine whether hyaluronic acid supplements can provide the same benefits.
However, since oral supplements boost the levels of hyaluronic acid found in the skin, it’s reasonable to suspect they may provide some benefit.
Hyaluronic acid is also found in the joints, where it keeps the space between your bones lubricated.
When the joints are lubricated, the bones are less likely to grind against each other and cause uncomfortable pain.
Hyaluronic acid supplements are very helpful for people with osteoarthritis, a type of degenerative joint disease caused by wear and tear on the joints over time.
Taking 80–200 mg daily for at least 2 months has been shown to significantly reduce knee pain in people with osteoarthritis, especially those between the ages of 40 and 70 years old.
Hyaluronic acid can also be injected directly into the joints for pain relief. However, an analysis of over 21,000 adults found only a small reduction in pain and a greater risk of adverse effects.
Some research shows that pairing oral hyaluronic acid supplements with injections can help extend pain-relieving benefits and increase the amount of time between shots.
New research shows hyaluronic acid supplements may help reduce symptoms of acid reflux.
When acid reflux occurs, the contents of the stomach are regurgitated up into the throat, causing pain and damage to the lining of the esophagus.
Hyaluronic acid may help soothe the damaged lining of the esophagus and speed up the recovery process.
One 2012 test-tube study found that applying a mixture of hyaluronic acid and chondroitin sulfate to acid-damaged throat tissue helped it heal much faster than when no treatment was used.
Human studies have also shown benefits.
One study found that taking a hyaluronic acid and chondroitin sulfate supplement along with an acid-reducing medication decreased reflux symptoms 60% more than taking acid-reducing medication alone.
Another older study showed that the same type of supplement was five times more effective at reducing acid reflux symptoms than a placebo.
Research in this area is still relatively new, and more studies are needed to replicate these results.
Nevertheless, these outcomes are promising.
Approximately 11% older adults experience symptoms of dry eye due to reduced tear production or tears evaporating too quickly.
Since hyaluronic acid is excellent at retaining moisture, it’s often used to treat dry eye.
Eye drops containing 0.2–0.4% hyaluronic acid have been shown to reduce dry eye symptoms and improve eye health.
Contact lenses that contain slow-release hyaluronic acid are also being developed as a possible treatment for dry eye.
In addition, hyaluronic acid eye drops are frequently used during eye surgery to reduce inflammation and speed wound healing.
While applying them directly to the eyes has been shown to reduce dry eye symptoms and improve overall eye health, it is unclear whether oral supplements have the same effects.
One small study in 24 people found that combining topical and oral hyaluronic acid was more effective at improving symptoms of dry eye than topical hyaluronic acid alone.
However, more large, high-quality studies are needed to understand the effects of oral hyaluronic acid supplements on eye health.
New animal research has begun to investigate the effects of hyaluronic acid supplements on bone health.
Two older studies have found that hyaluronic acid supplements can help slow the rate of bone loss in rats with osteopenia, the beginning stage of bone loss that precedes osteoporosis.
Some older test-tube studies have also shown that high doses of hyaluronic acid can increase the activity of osteoblasts, the cells responsible for building new bone tissue.
While more high quality, recent research in humans is needed, early animal and test-tube studies are promising.
Approximately 3–6% of females suffer from a condition called interstitial cystitis, or painful bladder syndrome.
This disorder causes abdominal pain and tenderness, along with a strong and frequent urge to urinate.
While the causes of interstitial cystitis are unknown, hyaluronic acid has been found to help relieve the pain and urinary frequency associated with this condition when inserted directly into the bladder through a catheter.
It’s unclear why hyaluronic acid helps relieve these symptoms, but researchers hypothesize that it helps repair damage to bladder tissue, making it less sensitive to pain.
Studies have not yet determined whether oral hyaluronic acid supplements can increase amounts of it in the bladder enough to have the same effects.
Hyaluronic acid supplements can be safely taken by most people and provide many health benefits.
Hyaluronic acid is well known for its skin benefits, especially alleviating dry skin, reducing the appearance of fine lines and wrinkles, and speeding up wound healing.
Hyaluronic acid can also help relieve joint pain in people with osteoarthritis.
Other notable applications include hyaluronic acid eye drops to relieve dry eye and inserting hyaluronic acid directly into the bladder via catheter to reduce pain.
Overall, hyaluronic acid is a beneficial supplement for a variety of conditions, especially those related to skin and joint health.
Hyaluronic acid is a water-binding molecule (formally known as a type of glycosaminoglycan) found abundantly in the skin.
Hyaluronic acid works by attracting large amounts of water molecules and holding them in the skin, which is essential for maintaining skin hydration and plumpness.
Hyaluronic Acid, also known as Hyaluron or Hyaluronan, helps skin retain moisture and serves as an anti-ageing agent ingredient in care products.
Hyaluronic acid comes in either a long-chain or short-chain form, which has different effects.
Building a face care routine using products with Hyaluronic Acid can effectively smooth fine lines and wrinkles.
Hyaluronic acid is a gel-like substance that is naturally present in the human body, namely in the skin, joints, eyes and connective tissue.
Capable of holding over 1,000 times its weight in water, it plays an important role in helping to retain moisture.
Due to these properties, it works wonderfully as an anti-ageing component in face creams and serums to keep skin soft and supple.
You may also see it under the names Hyaluron or Hyaluronan.
Hyaluronic acid production declines as people age, leading to moisture loss, volume reduction, and fine lines.
At around age 25, the skin's Hyaluronic Acid synthesis begins to slow, resulting in increased ageing signs.
Hyaluronic acid is an important part of the skin and the synovial fluid a main component of the joint fluid.
If there are problems with the joints in old age, it might be used to help. Of course, you should discuss this with your doctor for tailored advice.
Hyaluronic acid (HA) is an unsulfated glycosaminoglycan that is a ubiquitious component of the extracellular matrix.
This chapter first introduces the chemical structure, biophysical properties, and the biological context of Hyaluronic acid.
Next, the production of Hyaluronic acid from vertebrate, bacterial sources, and chemoenzymatic sources is described, along with relevant analytical methods and standards.
Then, methods for chemical modification of HA are described, in which HA is converted to a wide variety of biomaterials for clinical and research use.
The medical applications of Hyaluronic acid are then surveyed, including ophthalmic surgery, injections for osteoarthritis and dermal fillers, wound healing, and use in cell therapy and tissue engineering.
The final section describes resources available to Hyaluronic acid researchers and discusses the future of Hyaluronic acid science.
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). Hyaluronic acid (HA) content varies widely in different joints and species.
Hyaluronic acid is a non-sulfated, naturally occurring non-protein glycosaminoglycan (GAG), with distinct physico-chemical properties, produced by synoviocytes, fibroblasts, and chondrocytes.
Hyaluronic acid has an important role in the biomechanics of normal SF, where it is partially responsible for lubrication and viscoelasticity of the SF.
The concentration of Hyaluronic acid and its molecular weight (MW) decline as osteoarthritis (OA) progresses with aging. For that reason, Hyaluronic acid has been used for more than four decades in the treatment of OA in dogs, horses and humans.
Hyaluronic acid produces anti-arthritic effects via multiple mechanisms involving receptors, enzymes and other metabolic pathways.
Hyaluronic acid is also used in the treatment of ophthalmic, dermal, burns, wound repair, and other health conditions. The MW of Hyaluronic acid appears to play a critical role in the formulation of the products used in the treatment of diseases.
This review provides a mechanism-based rationale for the use of HA in some disease conditions with special reference to OA.
Introduction
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”.
The term “hyaluronan” was introduced in 1986 to conform to polysaccharide nomenclature. Subsequently, it was found in other organs (joints, skin, rooster comb, human umbilical cord, etc.) and tissues (connective, epithelial, and nervous).
Hyaluronic acid (HA) is also produced via microbial (Streptococcus zooepidemicus, Escherichia coli, Bacillus subtilis, and others) fermentation, and its molecular weight (MW) is reported to be controlled by UDP-N-acetylglucosamine concentration.
In both vertebrates and bacteria, its chemical structure is identical.
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.
Hyaluronic acid is a major component of the extracellular matrix (ECM) and is normally present in mammalian bone marrow, articular cartilage, and synovial fluid.
The first therapeutic injections of HA in animal joints were performed on track horses for traumatic arthritis.
This treatment proved effective and since then it has been widely used in veterinary medicine.
Currently, elastoviscous Hyaluronic acid solutions and its derivatives (such as Hylans) are commonly used in animals for treatment of arthritic pain.
Hyaluronic acid 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.
Hyaluronic acid has recently become more widely accepted in the armamentarium of therapies for OA pain.
In humans, HA has been used since the 1970s for treating joint pain and other health conditions.
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 Hyaluronic acid.
Physico-Chemical Properties and Physiological Functions
Hyaluronic acid (HA) is a naturally occurring non-sulfated glycosaminoglycan (GAG) non-protein compound with distinct physico-chemical properties of repeating β-1,4-D-glucuronic acid and β-1,3-N-acetylglucosamine units.
Hyaluronic acid has excellent viscoelasticity, high moisture retention capacity, high biocompatibility, and hygroscopic properties.
At a concentration as low as 0.1%, Hyaluronic acid chains can provide high viscosity.
By having these properties, Hyaluronic acid acts as a lubricant, shock absorber, joint structure stabilizer, and water balance- and flow resistance-regulator.
A 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.
Out of 15 g total Hyaluronic acid, 5 g turns over daily.
The greatest amount of Hyaluronic acid is present in the skin (about half of the total Hyaluronic acid, synovial fluid, the vitreous body, and the umbilical cord.
Hyaluronic acid is an important constituent of ECM and contributes to cell proliferation, migration, and morphogenesis (10, 36–38). HA also occurs within cells and it has been reported to have roles inside the cell.
Within the joint cavity, HA molecules are predominately synthesized by type B synoviocytes.
Hyaluronic acid (a polymer of disaccharides) can be 25,000 disaccharide repeats in length with a MW of 5,000–20,000,000 Da.
Hyaluronic acid is synthesized by hyaluronan synthase (HAS), of which vertebrates have three isozymes (HAS-1, HAS-2, and HAS-3).
These three HAS isozymes produce different size Hyaluronic acid polymers and are differentially regulated by transcriptional, translational and post-translational levels, including alternative splicing, sub-cellular localization and epigenetic processes.
These isoenzymes lengthen Hyaluronic acid by repeatedly adding glucuronic acid and N-acetylglucosamine to the nascent polysaccharide.
The three genes are located on three different chromosomes, even though they have 50–71% identity. They occur at 19q13.4, 8q24.12, and 16q22.1, respectively.
Hyaluronic acid is catabolized by hyaluronidases, and the MW of Hyaluronic acid in cartilage is reported to decrease with age.
Hyaluronic acid binds to ECM molecules and cell surface receptors, thereby regulating cellular behavior via control of the tissue's macro- and micro-environments.
In an in vitro study, Sommarin and Heinegård investigated the interaction between Hyaluronic acid and exogenous sulfate labeled cartilage proteoglycans (PGs) at the calf articular-cartilage chondrocyte cell surface.
Findings revealed that PGs interact with Hyaluronic acid receptors at the cell surface in the HA-binding region.
The bound Sulfate labeled PGs are located at the cell surface, and only small proportions of the PGs are internalized.
Hyaluronic acid can bind to three main classes of cell surface receptors: CD44 (a membrane glycoprotein), receptor for hyaluronate-mediated motility (RHAMM), and Intercellular Adhesion Molecule 1 (ICAM-1), which perform different functions.
CD44 is the most widely distributed cell surface receptor recognized for Hyaluronic acid binding.
CD44 interacts with a number of other ligands including osteopontin, collagens and matrix metalloproteinases (MMPs).
Hyaluronic acid may inhibit signal transduction through CD44 and RHAMM Hyaluronic acid receptors.
Hyaluronic acid is reported that higher- and lower- MW HA have distinct molecular and cellular mechanisms and diverse biological effects through interaction with CD44 receptors.
CD44-mediated signaling affects both chondrocyte survival pathways as well as apoptotic (chondroptotic) pathways.
Fragments of HA produced in free radical processes have the potential to augment the production of nitric oxide in a CD44-dependent mechanism.
In regard to defining functional chondrocyte CD44, future studies need to include analysis of the variant CD44 isoforms expression, phosphorylation, cytoskeletal interactions, occupancy, and turnover.
In addition to these receptors, two other receptors have been identified for Hyaluronic acid binding: lymphatic vessel endothelial hyaluronan receptor (LYVE-1), and hyaluronic acid receptor for endocytosis (HARE), also known as Stabilin-2.
Physiological roles of Hyaluronic acid are well-characterized in body tissues and fluids.
In general, Hyaluronic acid may be involved in various cellular interactions (cell differentiation, proliferation, development, and recognition) and physiological functions (lubrication, hydration balance, matrix structure, and steric interactions).
By having unique rheological properties and being a constituent of GAG and articular cartilage, the physiological roles of Hyaluronic acid are well-explained in normal structure and function of joints.
The physiological relevance of Hyaluronic acid is not only recognized in healthy and OA joints, but also in other tissues and health conditions.
Hyaluronic acid is a non-sulphated GAG and is composed of repeating polymeric disaccharides of D-glucuronic acid and N-acetyl-D-glucosamine linked by a glucuronidic β (1→3) bond.
In aqueous solutions Hyaluronic acid forms specific stable tertiary structures.
Despite the simplicity in its composition, without variations in its sugar composition or without branching points, Hyaluronic acid has a variety of physicochemical properties.
Hyaluronic acid polymers occur in a vast number of configurations and shapes, depending on their size, salt concentration, pH, and associated cations.
Unlike other GAG, Hyaluronic acid is not covalently attached to a protein core, but it may form aggregates with proteoglycans.
Hyaluronic acid encompasses a large volume of water giving solutions high viscosity, even at low concentrations.
Tissue and cell distribution of Hyaluronic acid
HA is widely distributed, from prokaryotic, to eukaryotic cells.
In humans, Hyaluronic acid is most abundant in the skin, accounting for 50% of the total body Hyaluronic acid, the vitreous of the eye, the umbilical cord, and synovial fluid, but it is also present in all tissues and fluids of the body, such as skeletal tissues, heart valves, the lung, the aorta, the prostate, tunica albuginea, corpora cavernosa and corpus spongiosum of the penis.
Hyaluronic acid is produced primarily by mesenchymal cells but also by other cell types.
Biological function of Hyaluronic acid
Over the past two decades there was considerable evidence presented that unraveled the functional role of Hyaluronic acid in molecular mechanisms and indicated the potential role of Hyaluronic acid for the development of novel therapeutic strategies for many diseases.
Functions of Hyaluronic acid include the following: hydration, lubrication of joints, a space filling capacity, and the framework through which cells migrate.
The synthesis of Hyaluronic acid increases during tissue injury and wound healing and Hyaluronic acid regulates several aspects of tissue repair, including activation of inflammatory cells to enhance immune response and the response to injury of fibroblasts49,50 and epithelial cells.
Hyaluronic acid also provides the framework for blood vessel formation and fibroblast migration, that may be involved in tumor progression.
The correlation of Hyaluronic acid levels on the cell surface of cancer cells with the aggressiveness of tumors has also been reported.
The size of Hyaluronic acid appears to be of critical importance for its various functions described above.
Hyaluronic acid of high molecular size, usually in excess of 1,000 kDa, is present in intact tissues and is antiangiogenic and immunosuppressive, whereas smaller polymers of Hyaluronic acid are distress signals and potent inducers of inflammation and angiogenesis.
Biosynthesis of Hyaluronic acid
Hyaluronic acid is synthesized by specific enzymes called Hyaluronic acid synthases (HAS).
These are membrane bound enzymes that synthesize Hyaluronic acid on the inner surface of the plasma membrane and then Hyaluronic acid is extruded through pore like structures into the extracellular space.
There are three mammalian enzymes HAS -1, -2 and -3, which exhibit distinct enzymatic properties and synthesize Hyaluronic acid chains of various length.
The use of biotinylated Hyaluronic acid-binding peptide revealed that not only cells of mesenchymal origin were capable of synthesizing Hyaluronic acid and permitted the histolocalization of Hyaluronic acid in the dermal compartment of skin and the epidermis.
This technique enabled the visualization of Hyaluronic acid in the epidermis, mainly in the ECM of the upper spinous and granular layers, whereas in the basal layer Hyaluronic acid is predominantly intracellular.
The function of the skin as a barrier is partly attributed to the lamellar bodies, thought to be modified lysosomes containing hydrolytic enzymes.
They fuse with the plasma membranes of mature keratinocytes and they have the ability to acidify via proton pumps and partially convert their polar lipids into neutral lipids.
Diffusion of aqueous material through the epidermis is blocked by these lipids synthesized by keratinocytes in the stratum granulosum.
This boundary effect corresponds to the level of Hyaluronic acid staining.
The Hyaluronic acid rich area inferior to this layer may obtain water from the moisture-rich dermis, and the water contained therein cannot penetrate beyond the lipid-rich stratum granulosum.
The hydration of the skin critically depends on the Hyaluronic acid bound water in the dermis and in the vital area of the epidermis, while maintenance of hydration essentially depends on the stratum granulosum.
Extensive loss of the stratum granulosum in patients with burns may cause serious clinical problems due to dehydration.
As mentioned above, skin Hyaluronic acid accounts for most of 50% of total body Hyaluronic acid.
The Hyaluronic acid content of the dermis is significantly higher than that of the epidermis, while papillary dermis has much greater levels of HA than reticular dermis.
The Hyaluronic acid of the dermis is in continuity with the lymphatic and vascular systems.
Hyaluronic acid in the dermis regulates water balance, osmotic pressure and ion flow and functions as a sieve, excluding certain molecules, enhancing the extracellular domain of cell surfaces and stabilizes skin structures by electrostatic interactions.
Elevated levels of Hyaluronic acid are synthesized during scar free fetal tissue repair and the prolonged presence of Hyaluronic acid assures such scar
free tissue repair.
Dermal fibroblasts provide the synthetic machinery for dermal Hyaluronic acid and should be the target for pharmacologic attempts to enhance skin hydration.
Unfortunately, exogenous Hyaluronic acid is cleared from the dermis and is rapidly degraded.
Hyaluronic acid synthases in the skin
In the skin, gene expression of HAS-1 and HAS-2 in the dermis and epidermis is differentially upregulated by TGF-β1, indicating that HAS isoforms are independently regulated and that the function of Hyaluronic acid is different in the dermis and the epidermis.
The mRNA expression of HAS-2 and HAS-3 can be stimulated by keratinocyte growth factor, which activates keratinocyte migration and stimulates wound healing, leading to the accumulation of intermediate-sized Hyaluronic acid in the culture medium and within keratinocytes.
The migratory response of keratinocytes in wound healing is stimulated by increased synthesis of Hyaluronic acid.
HAS-2 mRNA is also induced by IL-1β and TNFα in fibroblasts and by epidermal growth factor in rat epidermal keratinocytes.
Dysregulated expression of Hyaluronic acid synthases has been reported during tissue injury.
HAS-2 and HAS-3 mRNA are significantly increased after skin injury in mice, leading to increased epidermal Hyaluronic acid.
In juvenile hyaline fibromatosis, which is a rare autosomal recessive disease characterized by deposition of hyaline material and multiple skin lesions, there is a significant decreased expression of HAS-1 and HAS-3, accounting for the reduced synthesis of Hyaluronic acid in skin lesions.
In dermal fibroblasts, where the HAS-2 is the predominant isoform, glucocorticoids inhibit HAS mRNA almost completely, suggesting a molecular basis of the decreased Hyaluronic acid in atrophic skin as a result of local treatment with glucocorticoids.
Hyaluronidases in the skin
In the skin, it has not been established which of the various HYAL controls the turnover of Hyaluronic acid in the dermis and the epidermis.
The elucidation of the biology of HYAL in the skin may offer novel pharmacological targets to confront age related turnover of HA in skin.
Hyaluronic acid receptors in the skin
In the dermis and epidermis Hyaluronic acid is co-localized with CD44.
However, the exact CD44 variants in the different skin compartments have not yet been elucidated. CD44-HA interactions have been reported to mediate the binding of Langerhans cells to Hyaluronic acid in the matrix surrounding keratinocytes by their CD44-rich surfaces, as they migrate through the epidermis.
RHAMM is also expressed in the human skin.
The TGF-β1 induced stimulation of fibroblast locomotion is mediated via RHAMM, while overexpression of RHAMM can lead to the transformation of fibroblasts.108
Hyaluronic acid and skin aging
The most dramatic histochemical change observed in senescent skin is the marked disappearance of epidermal Hyaluronic acid, while Hyaluronic acid is still present in the dermis.
The reasons for this change in Hyaluronic acid homeostasis with aging is unknown.
As mentioned above, the synthesis of epidermal Hyaluronic acid is influenced by the underlying dermis and is under separate controls from the synthesis of dermal Hyaluronic acid.
Progressive reduction of the size of the HA polymers in skin as a result of aging has also been reported.
Thus, the epidermis loses the principle molecule responsible for binding and retaining water molecules, resulting in loss of skin moisture.
In the dermis, the major age-related change is the increasing avidity of Hyaluronic acid with tissue structures with the concomitant loss of Hyaluronic acid extractability.
This parallels the progressive cross-linking of collagen and the steady loss of collagen extractability with age.
All of the above age related phenomena contribute to the apparent dehydration, atrophy and loss of elasticity that characterizes aged skin.
Premature aging of skin is the result of repeated and extended exposure to UV radiation.
Approximately 80% of facial skin aging is attributed to UV-exposure.
UV radiation damage causes initially a mild form of wound healing and is associated at first with an increase of dermal Hyaluronic acid.
As little as 5 min of UV exposure in nude mice caused enhanced deposition of Hyaluronic acid, indicating that UV radiation induced skin damage is an extremely rapid event.
The initial redness of the skin following exposure to UV radiation may be due to a mild edematous reaction induced by the enhanced Hyaluronic acid deposition and histamine release.
Repeated and extensive exposures to UV ultimately simulate a typical wound healing response with deposition of scar like type I collagen, rather than the usual types I and III collagen mixture that gives skin resilience and pliability.
In the skin, photoaging results in abnormal GAG content and distribution compared with that found in scars, or in the wound healing response, with diminished Hyaluronic acid and increased levels of chondroitin sulfate proteoglycans.
In dermal fibroblasts this reduction in Hyaluronic acid synthesis was attributed to collagen fragments, which activate αvβ3-integrins and in turn inhibit Rho kinase signaling and nuclear translocation of phosphoERK, resulting in reduced HAS-2 expression.
We have recently unraveled some of the biochemical changes that may distinguish photoaging and natural aging.
Using photoexposed and photoprotected human skin tissue specimens, obtained from the same patient, we have shown a significant increase in the expression of HA of lower molecular mass in photoexposed skin, as compared with photoprotected skin.
This increase of degraded Hyaluronic acid was associated with a significant decrease in the expression of HAS-1 and an increased expression of HYAL-1, -2 and -3.
Furthermore, the expression of Hyaluronic acid receptors CD44 and RHAMM was significantly downregulated in photoexposed, as compared with photoprotected skin.
These findings indicate that photoexposed skin, and therefore extrinsic skin aging, is characterized by distinct homeostasis of Hyaluronic acid.
We have also assessed photoprotected skin tissue specimens from adults and juvenile patients and observed that intrinsic skin aging was associated with a significant reduction in the content of Hyaluronic acid and down regulation of HAS-1, HAS -2, CD44 and RHAMM.
Similar results for photoprotected skin have also been reported for both genders for HA, HAS-2 and CD44.
Conclusion
The available data suggest that Hyaluronic acid homeostasis exhibits a distinct profile in intrinsic skin aging, which is totally different of that in extrinsic skin aging.
Additional insight needs to be gained in understanding the metabolism of Hyaluronic acid in skin layers and the interactions of Hyaluronic acid with other skin components.
Such information will facilitate the ability to modulate skin moisture in a rational manner and may contribute to the refinement of current drugs and the development of novel treatments for skin aging.
