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82-539: 15587 ENSG00000068001 ENSMUSG00000010047 Q12891 O35632 NM_003773 NM_033158 NM_010489 NP_003764 NP_149348 NP_034619 Hyaluronidase-2 is a multifunctional protein, previously thought to only possess acid-active hyaluronan -degrading enzymatic function. In humans it is encoded by the HYAL2 gene . This gene encodes a protein which is similar in structure to hyaluronidases . Hyaluronidases intracellularly degrade hyaluronan , one of
164-699: A chaperone molecule , which releases the precursor molecule upon contact with a fiber of mature elastin. Tropoelastins are then deaminated to become incorporated into the elastin strand. Disorders such as cutis laxa and Williams syndrome are associated with deficient or absent elastin fibers in the ECM. In 2016, Huleihel et al., reported the presence of DNA, RNA, and Matrix-bound nanovesicles (MBVs) within ECM bioscaffolds. MBVs shape and size were found to be consistent with previously described exosomes . MBVs cargo includes different protein molecules, lipids, DNA, fragments, and miRNAs. Similar to ECM bioscaffolds, MBVs can modify
246-399: A gene on human chromosome 3 is a stub . You can help Misplaced Pages by expanding it . Hyaluronic acid Hyaluronic acid ( / ˌ h aɪ . ə l j ʊəˈr ɒ n ɪ k / ; abbreviated HA ; conjugate base hyaluronate ), also called hyaluronan , is an anionic , nonsulfated glycosaminoglycan distributed widely throughout connective , epithelial , and neural tissues . It
328-585: A matrix of glycoproteins , including hemicellulose , pectin , and extensin . The components of the glycoprotein matrix help cell walls of adjacent plant cells to bind to each other. The selective permeability of the cell wall is chiefly governed by pectins in the glycoprotein matrix. Plasmodesmata ( singular : plasmodesma) are pores that traverse the cell walls of adjacent plant cells. These channels are tightly regulated and selectively allow molecules of specific sizes to pass between cells. The extracellular matrix functionality of animals (Metazoa) developed in
410-406: A bifunctional crosslinking agent 1,4-Butanediol diglycidyl ether (BDDE) using a ResonantAcoustic mixer over a period of time ranging from about 1 minute to about 10 minutes. 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. Extracellular matrix In biology ,
492-410: A cosmetic filler. 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
574-469: 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). Hyaluronic acid can also be crosslinked with
656-447: A receptor for the oncogenic virus Jaagsiekte sheep retrovirus. The gene is one of several related genes in a region of chromosome 3p21.3 associated with tumor suppression . This gene encodes two alternatively spliced transcript variants which differ only in the 5' UTR. One study found associations between cleft lip and palate and mutations in the HYAL2 gene. An investigation published in 2017, attributed an additional function to
738-471: A reorganization of the cell's cytoskeleton to facilitate cell movement. Fibronectins are secreted by cells in an unfolded, inactive form. Binding to integrins unfolds fibronectin molecules, allowing them to form dimers so that they can function properly. Fibronectins also help at the site of tissue injury by binding to platelets during blood clotting and facilitating cell movement to the affected area during wound healing. Laminins are proteins found in
820-562: A role in innate immunity . There are limitations including the in vivo loss of this compound limiting the duration of effect. 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
902-675: A specific transmembrane receptor, CD44 . Collagen is the most abundant protein in the ECM, and is the most abundant protein in the human body. It accounts for 90% of bone matrix protein content. Collagens are present in the ECM as fibrillar proteins and give structural support to resident cells. Collagen is exocytosed in precursor form ( procollagen ), which is then cleaved by procollagen proteases to allow extracellular assembly. Disorders such as Ehlers Danlos Syndrome , osteogenesis imperfecta , and epidermolysis bullosa are linked with genetic defects in collagen-encoding genes . The collagen can be divided into several families according to
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#1732859603735984-400: A subject of research because of its impact on differentiation and cancer progression. In the brain, where hyaluronan is the main ECM component, the matrix displays both structural and signaling properties. High-molecular weight hyaluronan acts as a diffusional barrier that can modulate diffusion in the extracellular space locally. Upon matrix degradation, hyaluronan fragments are released to
1066-402: A type of ECM: collagen fibers and bone mineral comprise the ECM of bone tissue ; reticular fibers and ground substance comprise the ECM of loose connective tissue ; and blood plasma is the ECM of blood . The plant ECM includes cell wall components, like cellulose, in addition to more complex signaling molecules. Some single-celled organisms adopt multicellular biofilms in which
1148-486: 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
1230-494: Is a common ingredient in skin care products. Hyaluronic acid is used as a dermal filler in cosmetic surgery. It 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
1312-418: Is a linear polysaccharide found in all animal tissues. It occurs as a proteoglycan (PG) in which two or three HS chains are attached in close proximity to cell surface or ECM proteins. It is in this form that HS binds to a variety of protein ligands and regulates a wide variety of biological activities, including developmental processes , angiogenesis , blood coagulation , and tumour metastasis . In
1394-535: Is a linear glycosaminoglycan (GAG), an anionic, gel-like, polymer, found in the extracellular matrix of epithelial and connective tissues of vertebrates. It 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
1476-418: Is a notable exception; see below). Proteoglycans have a net negative charge that attracts positively charged sodium ions (Na ), which attracts water molecules via osmosis, keeping the ECM and resident cells hydrated. Proteoglycans may also help to trap and store growth factors within the ECM. Described below are the different types of proteoglycan found within the extracellular matrix. Heparan sulfate (HS)
1558-474: 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. Hyaluronic acid (HA)
1640-400: Is also a component of the group A streptococcal extracellular capsule , and is believed to play a role in virulence . 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
1722-490: 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 tissue
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#17328596037351804-410: Is called durotaxis . The term was coined by Lo CM and colleagues when they discovered the tendency of single cells to migrate up rigidity gradients (towards more stiff substrates) and has been extensively studied since. The molecular mechanisms behind durotaxis are thought to exist primarily in the focal adhesion , a large protein complex that acts as the primary site of contact between the cell and
1886-449: Is currently being used regularly to treat ulcers by closing the hole in the tissue that lines the stomach, but further research is currently being done by many universities as well as the U.S. Government for wounded soldier applications. As of early 2007, testing was being carried out on a military base in Texas. Scientists are using a powdered form on Iraq War veterans whose hands were damaged in
1968-632: 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,
2050-413: Is due to the strong solvation of these molecules. 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
2132-434: Is feedback inhibition of hyaluronan synthesis by low-molecular-weight hyaluronan (<500 kDa) at high concentrations, but there is 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. A fasciacyte
2214-632: 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. 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. UDP-glucuronic acid and UDP-n-acetylglucosamine get bound together to form HA via hasA (HA synthase), completing
2296-539: 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. Due to its accumulation in airway epithelial cells in various respiratory diseases , such as COVID-19 , cystic fibrosis , influenza , and sepsis , hyaluronic acid
2378-438: Is indicated for carpal and fetlock joint dysfunctions, but not when joint sepsis or fracture are suspected. It is especially used for synovitis associated with equine osteoarthritis. It can be injected directly into an affected joint, or intravenously for less localized disorders. It may cause mild heating of the joint if directly injected, but this does not affect the clinical outcome. Intra-articularly administered medicine
2460-513: Is produced on a large scale by extraction from animal tissues, such as chicken comb , and from Streptococci . 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
2542-489: Is regulated by specific cell-surface cellular adhesion molecules (CAM) known as integrins . Integrins are cell-surface proteins that bind cells to ECM structures, such as fibronectin and laminin, and also to integrin proteins on the surface of other cells. Fibronectins bind to ECM macromolecules and facilitate their binding to transmembrane integrins. The attachment of fibronectin to the extracellular domain initiates intracellular signalling pathways as well as association with
HYAL2 - Misplaced Pages Continue
2624-436: 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. HA 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
2706-564: 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 HA. HA precursors are synthesized by first phosphorylating glucose by hexokinase, yielding glucose-6-phosphate, which
2788-402: Is the perfused , fibrous connective tissue that replaces a fibrin clot in healing wounds. It typically grows from the base of a wound and is able to fill wounds of almost any size it heals. HA is abundant in granulation tissue matrix. A variety of cell functions that are essential for tissue repair may attribute to this HA-rich network. These functions include facilitation of cell migration into
2870-490: Is the main HA precursor. Then, two routes are taken to synthesize UDP-n-acetylglucosamine and UDP-glucuronic acid which both react to form HA. 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). UDP-glucuronic acid
2952-424: Is thus found in abundance in the ECM of load-bearing joints. It is also a chief component of the interstitial gel. Hyaluronic acid is found on the inner surface of the cell membrane and is translocated out of the cell during biosynthesis. Hyaluronic acid acts as an environmental cue that regulates cell behavior during embryonic development, healing processes, inflammation , and tumor development. It interacts with
3034-444: Is under study as a possible mediator of lung inflammatory mechanisms, as of 2022. The high biocompatibility of hyaluronic acid and its common presence in the extracellular matrix of tissues indicate its possible use as a biomaterial scaffold in tissue engineering . In particular, research groups have found hyaluronan's properties for tissue engineering and regenerative medicine may be improved with cross-linking, producing
3116-451: 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 HA averages about 7 MDa per molecule, or about 20,000 disaccharide monomers, while other sources mention 3–4 MDa . Medically, hyaluronic acid is used to treat osteoarthritis of the knee, dry eye, for wound repair, and as
3198-501: 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
3280-403: The basal laminae of virtually all animals. Rather than forming collagen-like fibers, laminins form networks of web-like structures that resist tensile forces in the basal lamina. They also assist in cell adhesion. Laminins bind other ECM components such as collagens and nidogens . There are many cell types that contribute to the development of the various types of extracellular matrix found in
3362-471: The cornea , cartilage, bones , and the horns of animals . Hyaluronic acid (or "hyaluronan") is a polysaccharide consisting of alternating residues of D-glucuronic acid and N-acetylglucosamine, and unlike other GAGs, is not found as a proteoglycan. Hyaluronic acid in the extracellular space confers upon tissues the ability to resist compression by providing a counteracting turgor (swelling) force by absorbing significant amounts of water. Hyaluronic acid
HYAL2 - Misplaced Pages Continue
3444-541: The extracellular matrix ( ECM ), also called intercellular matrix (ICM), is a network consisting of extracellular macromolecules and minerals, such as collagen , enzymes , glycoproteins and hydroxyapatite that provide structural and biochemical support to surrounding cells. Because multicellularity evolved independently in different multicellular lineages, the composition of ECM varies between multicellular structures; however, cell adhesion, cell-to-cell communication and differentiation are common functions of
3526-426: 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
3608-730: The ECM can differ by several orders of magnitude. This property is primarily dependent on collagen and elastin concentrations, and it has recently been shown to play an influential role in regulating numerous cell functions. Cells can sense the mechanical properties of their environment by applying forces and measuring the resulting backlash. This plays an important role because it helps regulate many important cellular processes including cellular contraction, cell migration , cell proliferation , differentiation and cell death ( apoptosis ). Inhibition of nonmuscle myosin II blocks most of these effects, indicating that they are indeed tied to sensing
3690-434: The ECM can serve many functions, such as providing support, segregating tissues from one another, and regulating intercellular communication. The extracellular matrix regulates a cell's dynamic behavior. In addition, it sequesters a wide range of cellular growth factors and acts as a local store for them. Changes in physiological conditions can trigger protease activities that cause local release of such stores. This allows
3772-496: The ECM. The animal extracellular matrix includes the interstitial matrix and the basement membrane . Interstitial matrix is present between various animal cells (i.e., in the intercellular spaces). Gels of polysaccharides and fibrous proteins fill the interstitial space and act as a compression buffer against the stress placed on the ECM. Basement membranes are sheet-like depositions of ECM on which various epithelial cells rest. Each type of connective tissue in animals has
3854-465: The ECM. This complex contains many proteins that are essential to durotaxis including structural anchoring proteins ( integrins ) and signaling proteins (adhesion kinase ( FAK ), talin , vinculin , paxillin , α-actinin , GTPases etc.) which cause changes in cell shape and actomyosin contractility. These changes are thought to cause cytoskeletal rearrangements in order to facilitate directional migration . Due to its diverse nature and composition,
3936-594: The HA-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 HA 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 HA content, giving rise to increased tissue hydration. It has been suggested that
4018-530: The Hyaluronidase 2 (HYAL2) protein. The study found interactions between HYAL2 and proteins involved in the alternative splicing of CD44 pre-mRNA. Another study published in 2020, described roles for HYAL2 in the orchestration of cytoskeletal components involved in myofibroblast contraction. These recent discoveries suggest a broader regulatory role for the HYAL2 protein in cell biology. This article on
4100-409: The activation state of macrophages and alter different cellular properties such as; proliferation, migration and cell cycle. MBVs are now believed to be an integral and functional key component of ECM bioscaffolds. Fibronectins are glycoproteins that connect cells with collagen fibers in the ECM, allowing cells to move through the ECM. Fibronectins bind collagen and cell-surface integrins , causing
4182-420: 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
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#17328596037354264-429: The cell membrane into the extracellular space. The term fasciacyte was coined to describe fibroblast-like cells that synthesize HA. 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
4346-530: The cells are embedded in an ECM composed primarily of extracellular polymeric substances (EPS). Components of the ECM are produced intracellularly by resident cells and secreted into the ECM via exocytosis . Once secreted, they then aggregate with the existing matrix. The ECM is composed of an interlocking mesh of fibrous proteins and glycosaminoglycans (GAGs). Glycosaminoglycans (GAGs) are carbohydrate polymers and mostly attached to extracellular matrix proteins to form proteoglycans (hyaluronic acid
4428-413: The cellular cytoskeleton via a set of adaptor molecules such as actin . Extracellular matrix has been found to cause regrowth and healing of tissue. Although the mechanism of action by which extracellular matrix promotes constructive remodeling of tissue is still unknown, researchers now believe that Matrix-bound nanovesicles (MBVs) are a key player in the healing process. In human fetuses, for example,
4510-499: The destruction of extracellular matrix by enzymes such as serine proteases , threonine proteases , and matrix metalloproteinases . The stiffness and elasticity of the ECM has important implications in cell migration , gene expression, and differentiation . Cells actively sense ECM rigidity and migrate preferentially towards stiffer surfaces in a phenomenon called durotaxis . They also detect elasticity and adjust their gene expression accordingly, which has increasingly become
4592-477: The extracellular matrix are called ECM Biomaterial . Plant cells are tessellated to form tissues . The cell wall is the relatively rigid structure surrounding the plant cell . The cell wall provides lateral strength to resist osmotic turgor pressure , but it is flexible enough to allow cell growth when needed; it also serves as a medium for intercellular communication. The cell wall comprises multiple laminate layers of cellulose microfibrils embedded in
4674-494: 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
4756-407: The extracellular matrix serves two main purposes. First, it prevents the immune system from triggering from the injury and responding with inflammation and scar tissue. Next, it facilitates the surrounding cells to repair the tissue instead of forming scar tissue. For medical applications, the required ECM is usually extracted from pig bladders , an easily accessible and relatively unused source. It
4838-447: The extracellular matrix works with stem cells to grow and regrow all parts of the human body, and fetuses can regrow anything that gets damaged in the womb. Scientists have long believed that the matrix stops functioning after full development. It has been used in the past to help horses heal torn ligaments, but it is being researched further as a device for tissue regeneration in humans. In terms of injury repair and tissue engineering ,
4920-500: The extracellular matrix, especially basement membranes , the multi-domain proteins perlecan , agrin , and collagen XVIII are the main proteins to which heparan sulfate is attached. Chondroitin sulfates contribute to the tensile strength of cartilage, tendons , ligaments , and walls of the aorta . They have also been known to affect neuroplasticity . Keratan sulfates have a variable sulfate content and, unlike many other GAGs, do not contain uronic acid . They are present in
5002-425: The extracellular space, where they function as pro-inflammatory molecules, orchestrating the response of immune cells such as microglia . Many cells bind to components of the extracellular matrix. Cell adhesion can occur in two ways; by focal adhesions , connecting the ECM to actin filaments of the cell, and hemidesmosomes , connecting the ECM to intermediate filaments such as keratin . This cell-to-ECM adhesion
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#17328596037355084-449: 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
5166-407: The free-radical scavenging property of HA contributes to protection against solar radiation, supporting the role of CD44 acting as a HA receptor in the epidermis. Epidermal HA 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, HA is expressed in
5248-446: The late 1970s, intraocular lens implantation was often followed by severe corneal edema , due to endothelial cell damage during the surgery. It 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. Hyaluronan is used in treatment of articular disorders in horses , in particular those in competition or heavy work. It
5330-405: 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 HA 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
5412-485: The major glycosaminoglycans of the extracellular matrix. Hyaluronan is thought to be involved in cell proliferation, migration and differentiation. Varying functions have been described for this protein. It has been described as a lysosomal hyaluronidase which is active at a pH below 4 and specifically hydrolyzes high molecular weight hyaluronan. It has also been described as a GPI-anchored cell surface protein which does not display hyaluronidase activity but does serve as
5494-453: The mechanical properties of the ECM, which has become a new focus in research during the past decade. Differing mechanical properties in ECM exert effects on both cell behaviour and gene expression . Although the mechanism by which this is done has not been thoroughly explained, adhesion complexes and the actin - myosin cytoskeleton , whose contractile forces are transmitted through transcellular structures are thought to play key roles in
5576-419: 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
5658-471: 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 . Hyaluronic acid is derived from hyalos (Greek for vitreous, meaning ‘glass-like’) and uronic acid because it
5740-607: The plethora of tissue types. The local components of ECM determine the properties of the connective tissue. Fibroblasts are the most common cell type in connective tissue ECM, in which they synthesize, maintain, and provide a structural framework; fibroblasts secrete the precursor components of the ECM, including the ground substance . Chondrocytes are found in cartilage and produce the cartilaginous matrix. Osteoblasts are responsible for bone formation. The ECM can exist in varying degrees of stiffness and elasticity , from soft brain tissues to hard bone tissues. The elasticity of
5822-400: 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 is essential for the formation of granulation tissue. The early stage of granulation tissue
5904-400: The rapid local growth-factor-mediated activation of cellular functions without de novo synthesis. Formation of the extracellular matrix is essential for processes like growth, wound healing , and fibrosis . An understanding of ECM structure and composition also helps in comprehending the complex dynamics of tumor invasion and metastasis in cancer biology as metastasis often involves
5986-419: 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
6068-572: 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 . Hyaluronic acid is used to displace tissues away from tissues which are going to be subjected to radiation, for instance in one treatment option for some prostate cancers. Hyaluronic acid
6150-419: 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
6232-416: The synthesis. 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
6314-459: The types of structure they form: Elastins , in contrast to collagens, give elasticity to tissues, allowing them to stretch when needed and then return to their original state. This is useful in blood vessels , the lungs , in skin , and the ligamentum nuchae , and these tissues contain high amounts of elastins. Elastins are synthesized by fibroblasts and smooth muscle cells. Elastins are highly insoluble, and tropoelastins are secreted inside
6396-828: The war. Not all ECM devices come from the bladder. Extracellular matrix coming from pig small intestine submucosa are being used to repair "atrial septal defects" (ASD), "patent foramen ovale" (PFO) and inguinal hernia . After one year, 95% of the collagen ECM in these patches has been replaced by the body with the normal soft tissue of the heart. Extracellular matrix proteins are commonly used in cell culture systems to maintain stem and precursor cells in an undifferentiated state during cell culture and function to induce differentiation of epithelial, endothelial and smooth muscle cells in vitro. Extracellular matrix proteins can also be used to support 3D cell culture in vitro for modelling tumor development. A class of biomaterials derived from processing human or animal tissues to retain portions of
6478-669: The wound margin, in the connective tissue matrix, and collocating with CD44 expression in migrating keratinocytes. 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 HA could possibly cause adverse effects . A 2020 meta-analysis found that intra-articular injection of high molecular weight HA improved both pain and function in people with knee osteoarthritis. Hyaluronic acid has been used to treat dry eye . Hyaluronic acid
6560-724: The yet to be discovered molecular pathways. ECM elasticity can direct cellular differentiation , the process by which a cell changes from one cell type to another. In particular, naive mesenchymal stem cells (MSCs) have been shown to specify lineage and commit to phenotypes with extreme sensitivity to tissue-level elasticity. MSCs placed on soft matrices that mimic the brain differentiate into neuron -like cells, showing similar shape, RNAi profiles, cytoskeletal markers, and transcription factor levels. Similarly stiffer matrices that mimic muscle are myogenic, and matrices with stiffnesses that mimic collagenous bone are osteogenic. Stiffness and elasticity also guide cell migration , this process
6642-439: 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
6724-449: 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 . 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,
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