Hyaluronic acid Physiological and function

Hyaluronic acid  conjugated group hyaluronate),also known as hyaluronic acid,is an anionic,nonsulfated glycosaminoglycan,widely Distributed in connective tissue,epithelial tissue and nervous tissue.It is unique among glycosaminoglycans in that it is non-sulfated, forms in the plasma membrane rather than the Golgi apparatus, and can be very large: human synovial HA averages about 7 million daltons per molecule,or about 20,000 disaccharide monomers,while other sources mention 3-4 million Daltons.An average 70 kg (150 lb) human body contains approximately 15 grams of hyaluronic acid,one-third of which is metabolized (i.e.,degraded and synthesized) every day.As one of the main components of the extracellular matrix,it makes an important contribution to cell proliferation and migration,and is involved in the progression of many malignant tumors.Hyaluronic acid is also a component of the exosome of group A streptococcal bacteria,[9] and is thought to play a role in virulence.

Physiological function 

It wasn't until the late 1970s that hyaluronic acid was described as a "sticky" molecule,a ubiquitous carbohydrate polymer that is part of the extracellular matrix.For example, hyaluronic acid, a major component of synovial fluid, was found to increase the viscosity of synovial fluid.Along with lubricants,it is one of the main lubricating components of fluids.Hyaluronic acid is an important building block of articular cartilage,where it exists as a coating around each cell (chondrocyte).When aggrecan monomers bind to hyaluronic acid in the presence of HAPLN1 (hyaluronic acid and proteoglycan connexin 1),large, highly negatively charged aggregates are formed. These aggregates absorb water and are responsible for the elasticity of the cartilage (its resistance to compression). The molecular weight (size) of hyaluronic acid in cartilage decreases with age,but increases in quantity.A lubricating role of hyaluronan in muscle connective tissue has been proposed to enhance sliding between adjacent tissue layers.A specialized type of fibroblast, embedded in the dense fascial tissue, is thought to be specialized in the biosynthesis of hyaluronic acid-rich matrix.Their associated activity may involve regulating the ability to slide between adjacent muscle connective tissues.Hyaluronic acid is also a major component of the skin and is involved in the repair of tissue.When the skin is exposed to too much UVB rays,it becomes inflamed (sunburn), and the cells in the dermis stop producing as much hyaluronic acid and degrade it faster.Hyaluronic acid degradation products then accumulate in the skin after UV exposure.Although it is abundant in the extracellular matrix, hyaluronan also contributes to the tissue hydrodynamics,motility and proliferation of cells and is involved in the interaction of many cell surface receptors, particularly those including its primary receptors CD44 and Interaction of RHAMM.Upregulation of CD44 itself is widely accepted as a marker of cellular activation in lymphocytes.The contribution of hyaluronan to tumor growth may be due to its interaction with CD44.The receptor CD44 is involved in cell-adhesion interactions required by tumor cells.Although hyaluronan binds to the receptor CD44,there is evidence that hyaluronan degradation products transduce their inflammatory signals through Toll-like receptor 2 (TLR2), TLR4, or TLR2 and TLR4 in macrophages and dendritic cells.TLRs and hyaluronan play a role in innate immunity.There are limitations,including loss of the compound in vivo that limits the duration of action.

Wound repair

As a major component of the extracellular matrix, hyaluronic acid plays a key role in tissue regeneration, inflammatory responses,and angiogenesis,all phases of wound repair.However, as of 2016, reviews of its effects on wound healing in burns, diabetic foot ulcers, or surgical skin repairs show only limited positive clinical research evidence.Hyaluronic acid binds to water and swells to form a gel, making it useful in skin treatments as a dermal filler for facial wrinkles; its effects last about 6 to 12 months, and the treatment has been approved by the U.S.Food and Drug Administration. Regulatory Approval.

Granulation

Granulation tissue is perfused fibrous connective tissue that replaces fibrin clots in healing wounds.It usually grows from the bottom of the wound and is able to fill almost any size wound it heals.HA is abundant in the granulation tissue matrix.A variety of cellular functions essential for tissue repair may be attributed to this HA-rich network.These functions include promoting cell migration into the temporary wound matrix,cell proliferation, and tissue granulation tissue matrix.Initiation of inflammation is critical for the formation of granulation tissue; thus, as mentioned above,the pro-inflammatory effects of HA also contribute to this phase of wound healing.