Sodium hyaluronate is the salt form of hyaluronic acid. It is synthesized to create a smaller molecular structure for stability and increased resistance to oxidation. Sodium hyaluronate is usually used for anti-aging and moisturizing because of its ability to improve firmness levels, smooth out fine lines, and hydrate the skin. You can find sodium hyaluronate in many products, including serums and moisturizers.
It is also possible to take it as an oral supplement. What is the primary difference between hyaluronic acid and sodium hyaluronate? The biggest difference? Sodium hyaluronate has a smaller molecular size, which means that it can penetrate the skin better.
Other than that, they both offer the same benefits. Many makeup brands add one or both ingredients to their primers; because HA retains moisture so well, it makes skin look instantly plumper and more supple. Reduced fine lines and wrinkles As sodium hyaluronate and hyaluronic acid amplify skin hydration, skin regains a youthful plumpness and fine lines and wrinkles become less visible.
Geria adds. That stability makes sodium hyaluronate attractive to product formulators. To recap: hydrolyzed hyaluronic acid works at the surface-level to smooth and hydrate, and sodium hyaluronate does the same on a deeper level, which helps reduce signs of aging. Geria says. One study theorizes this is because the low molecular size of sodium hyaluronate can cause inflammation.
If you notice any inflammatory symptoms — blemishes, redness, irritation — you may want to hold off on the sodium hyaluronate serums and moisturizers to see if that helps. However, we may receive a portion of sales if you purchase a product through a link in this article. This article was originally published on 7. They may be similar, but the two are incredibly different. By Jessica DeFino. Updated: 4. Hydrolyzed hyaluronic acid keeps the skin's surface moisturized and smooth, while vitamin B5 stimulates cells' repair response.
It's made with two powerhouse ingredients to increase hydration: hydrolyzed hyaluronic acid and silver ear mushrooms. Because the residence time of exogenously administered HA in the joint is relatively short, HA probably has physiological effects in the joint that contribute to its effects in the joint over longer periods.
The exact mechanism s by which intra-articular HA or hylans relieve pain is currently unknown. Improvements in OA with administration of HA have been shown in both electrophysiology and animal pain model studies [ 15 — 17 ]; Gomis A, Pawlak M, Schmidt RF, Belmonte C: Effects of elastoviscous substances on the mechanosensitivity of articular pain receptors. HA treatment has also been shown to have protective effects on cartilage in experimental models of OA [ 18 — 20 ].
In vitro studies also show that HA has beneficial effects on the extracellular matrix, immune cells, and inflammatory mediators [ 21 — 26 ]. This article provides a brief introduction to the pathophysiology of OA and reviews the current scientific literature regarding the physiological effects of HA and hylans, focusing on antinociceptive effects, possible protective effects on cartilage, and effects on molecular and cellular factors involved in OA disease progression.
The effects of HA and hylans on these factors may provide insight into the mechanism by which HA and hylans elicit their clinical benefits. The following search words were used alone and in combination when appropriate: hyaluronan, hyaluronic acid, sodium hyaluronate, hylan, OA, knee, cartilage, synovium, pathophysiology, extracellular matrix, proteoglycans PGs , aggrecanase, inflammation, immunology, proteases, matrix metalloproteinases MMPs , cytokines, proinflammatory mediators, nitric oxide NO , prostaglandins, lymphocytes, nociceptors, and mechanoreceptors.
OA is characterized by a slow degradation of cartilage over several years. In normal cartilage, a delicate balance exists between matrix synthesis and degradation; in OA, however, cartilage degradation exceeds synthesis. The balance between synthesis and degradation is affected by age and is regulated by several factors produced by the synovium and chondrocytes, including cytokines, growth factors, aggrecanases, and MMPs [ 27 — 32 ] Fig.
Several factors contribute to the breakdown and synthesis of cartilage. In osteoarthritis OA , the balance between cartilage degradation and synthesis leans toward degradation. In addition to water, the extracellular matrix is composed of PGs entrapped within a collagenous framework or fibrillary matrix Fig.
PGs are made up of glycosaminoglycans attached to a backbone made of HA [ 33 ]. In OA, the collagen turnover rate increases, the PG content decreases, the PG composition changes, and the water content increases [ 33 ].
The size of HA molecules [ 3 ] and their concentration [ 34 ] in synovial fluid also decrease in OA. A significant PG in articular cartilage is aggrecan, which binds to HA and helps provide the compressibility and elasticity of cartilage [ 32 ].
Aggrecan is cleaved by aggrecanases, leading to its degradation and to subsequent erosion of cartilage [ 34 , 35 ]. The loss of aggrecan from the cartilage matrix is one of the first pathophysiological changes observed in OA [ 32 ].
The extracellular matrix of cartilage is composed of proteoglycans attached to a backbone of hyaluronic acid that is intertwined among collagen fibrils. Proteoglycans have both chondroitin-sulfate- and keratin-sulfate-rich regions, and link proteins facilitate binding of aggrecan to hyaluronic acid. Both cytokines have been shown to potently induce degradation of cartilage in vitro [ 31 ].
The production of the chemokine RANTES regulated upon activation, normal T-cell expressed and secreted , is also high in OA cartilage compared with normal cartilage, is stimulated by IL-1, and increases the release of PGs from cartilage [ 37 ]. Prostaglandins and leukotrienes may also be involved in cartilage destruction in OA. The extracellular matrix in cartilage is degraded by locally produced MMPs.
The activity of many MMPs increases in OA by either an increase in their own synthesis, an increased activation by their proenzymes, or decreased activity of their inhibitors [ 29 ]. To further exacerbate the degradative activity in OA, expression levels of tissue inhibitor of metalloproteinases TIMP -1 are reduced [ 29 ]. In an attempt to reverse the breakdown of the extracellular matrix, the chondrocytes increase synthesis of matrix components including PGs [ 29 ]. Even though this activity increases, a net loss of PG in the upper cartilage layer is seen, because the increased activity has been observed only in the middle and deeper layers of cartilage [ 29 ].
Local production of growth and differentiation factors such as insulin-like growth factor 1, transforming growth factors, fibroblastic growth factors, and bone morphogenetic proteins also stimulate matrix synthesis [ 29 , 41 ]. NO may be involved in cartilage catabolism by inhibiting the synthesis of collagen and PG, enhancing MMP activity, reducing the synthesis of an IL-1 receptor antagonist by chondrocytes, and increasing susceptibility to cell injury i.
NO can also inhibit the attachment of fibronectin to chondrocytes, thus enhancing PG synthesis [ 42 ]. Additionally, NO can induce apoptosis of chondrocytes in OA [ 30 ]. Chondrocyte apoptosis occurs in both human and experimental OA and is correlated with the severity of cartilage destruction [ 42 ]. Apoptosis of chondrocytes in OA has been shown to have a higher incidence in OA than in normal cartilage, to be present close to the articular surface, and to be significantly correlated with OA grade [ 43 , 44 ].
Death of chondrocytes could easily lead to reduced matrix production, since chondrocytes are the only source of matrix components and their population is not renewed [ 29 ]. Depletion of PGs was observed in cartilage areas that contained apoptotic chondrocytes [ 43 ].
Cellular products of apoptosis may also contribute to the pathophysiology of OA, because apoptotic cells are not effectively removed from cartilage [ 29 ] due to its avascular nature and can cause pathogenetic events such as abnormal cartilage calcification or extracellular matrix degradation [ 43 ].
HA is responsible for the viscoelastic quality of synovial fluid that acts as both a lubricant and shock absorber [ 3 ]. In synovial fluid, HA coats the surface of the articular cartilage and shares space deeper in the cartilage among collagen fibrils and sulfated PGs [ 3 ]. In this respect, HA probably protects the cartilage and blocks the loss of PGs from the cartilage matrix into the synovial space, maintaining the normal cartilage matrix [ 3 ].
Similarly, HA may also help prevent invasion of inflammatory cells into the joint space. In acute and chronic inflammatory processes of the joint, the size of HA molecules decreases at the same time as the number of cells in the joint space increases [ 3 ].
In synovial fluid from knee joints in OA, concentrations of HA, glycosaminoglycans, and keratan sulfate are lower than in synovial fluid from normal knee joints [ 34 ]. Exogenous HA may facilitate the production of newly synthesized HA. HA in the synovial fluid binds to chondrocytes via the CD44 receptor [ 46 , 47 ], supporting a role for HA in healthy cartilage.
When expression of CD44 was suppressed in bovine articular cartilage slices, a near-complete loss of PG staining was observed [ 48 ]. CD44 adhesion to HA has also been shown to mediate chondrocyte proliferation and function [ 49 ]. Relief of knee pain from OA with HA in clinical studies may be due to the effects of HA on nerve impulses and nerve sensitivity. Inflammation of the knee joint influences excitability of nociceptors of articular nerves [ 15 ]. In experimental OA, these nerves become hyperalgesic, spontaneously discharge, and are sensitive to non-noxious joint movements [ 15 ].
Administration of HA to isolated medial articular nerves from an experimental model of OA significantly decreased ongoing nerve activity as well as movement-evoked nerve activity [ 15 ].
These authors reported that HAs with lower MWs had either less of an effect or no effect on nerve impulse frequency. Mechanical forces on stretch-activated ion channels are involved in depolarization of the articular nerve terminal. In a rat model, HA improved the abnormal gait of rats with experimentally induced OA in a dose-dependent manner, indicating an antinociceptive effect of HA [ 16 ]. This effect may be mediated through the attenuation of prostaglandin E 2 PGE 2 and bradykinin synthesis, since HA inhibited their synthesis in a MW-dependent manner [ 16 ].
Further, HA has been shown to induce analgesia in a bradykinin-induced model of joint pain in rats [ 17 ]. This analgesic action was also MW-dependent, as significant effects were observed at lower concentrations with a higher-MW formulation than with lower-MW HAs [ 17 ]. Lastly, HA may have direct or indirect effects on substance P, which can be involved in pain [ 51 ]. Since substance P interacts with excitatory amino acids, prostaglandins, and NO, the effects of HA on these factors can indirectly affect the pharmacology of substance P [ 51 ].
Additionally, HA has been shown to inhibit an increased vascular permeability induced by substance P [ 51 ]. Many effects of exogenous HA on the extracellular matrix, inflammatory mediators, and immune cells have been reported in in vitro studies.
The influence of HA on these factors may contribute to cartilage protection in OA. In vitro experiments indicate that HA administration can enhance the synthesis of extracellular matrix proteins, including chondroitin and keratin sulfate, and PGs Table 2. In rabbit chondrocytes cultured on collagen gels, HA increased the synthesis of the glycosaminoglycan chondroitin sulfate [ 52 ].
Release of keratan sulfate, a PG fragment, into synovial fluid is also suppressed by HA in an ovine model [ 53 ]. Beneficial effects on PG synthesis have also been demonstrated in vitro with HA. This glycosaminoglycan has been shown to increase PG synthesis in equine articular cartilage [ 22 ], rabbit chondrocytes [ 55 ], and bovine articular cartilage treated with IL-1, which has been shown to reduce PG synthesis in vitro [ 56 ].
HA has also been shown to suppress the release of PGs from rabbit chondrocytes [ 19 , 59 ] and bovine articular cartilage [ 60 ] in the absence and in the presence of IL Additionally, resorption of PGs from cartilage explants was inhibited with hylan; in these experiments, high-viscosity hylan was more effective than a low-viscosity form [ 61 ]. In an in vivo model of canine OA, a reduced amount of glycosaminoglycan release was found in hyaluronate-treated joints compared with an increased release in untreated joints [ 63 ].
HA has also been shown to suppress cartilage damage by fibronectin fragments in vitro and in vivo. Fragments of fibronectin bind and penetrate cartilage and subsequently increase levels of MMPs and suppress PG synthesis [ 64 ]. In explant cultures of human cartilage, HA blocked PG depletion induced by fibronectin fragments [ 65 ]. This protective effect was associated with its coating of the articular surface, suppression of fibronectin-fragment-enhanced stromelysin-1 release, increased PG synthesis, and restoration of PGs in damaged cartilage [ 65 ].
Similar effects of HA on PGs were observed in bovine articular cartilage in vitro: HA suppressed fibronectin-fragment-mediated PG depletion and partially restored PGs in the damaged cartilage [ 64 ]. HA also attenuated the enhanced stromelysin-1 release induced with fragments of fibronectin [ 64 ]. When fibronectin fragments were intra-articularly administered into rabbit knees, the decrease in PG content was reduced with HA [ 66 ].
HA has significant effects on inflammatory mediators, including cytokines, proteases and their inhibitors, and prostaglandins Table 3 , that may translate into cartilage protection. In vitro studies show that HA alters the profile of inflammatory mediators such that the balance between cell matrix synthesis and degradation is shifted away from degradation. Although HA also stimulated stromelysin activity in the same study, the increase was inconsistent and was less with a high-MW than with a low-MW HA [ 68 ].
The plasminogen activator system, shown to be active in synovial fibroblasts of rheumatoid arthritis RA , is also influenced by HA [ 24 ]. In synovial fibroblasts from OA and RA patients, HA reduced the secreted antigen and activity of urokinase plasminogen activator, as well as its receptor [ 24 ]. Similarly, intra-articular administration of HA decreased urokinase plasminogen activator activity in the synovial fluid of patients who showed clinical improvement [ 69 ].
Metabolites of arachidonic acid such as various prostaglandins mediate, in part, inflammatory responses. HA also has antioxidant effects in various systems. Most recently, in an in vitro assay it showed such effects that were both MW- and dose-dependent [ 75 ].
Using two different antioxidant models, Sato and colleagues found that both HA and one of its components, D-glucuronic acid, reduced the amount of reactive oxygen species [ 76 ]. Interleukininduced oxidative stress [ 77 ] and superoxide anion [ 78 ] in bovine chondrocytes were also reduced with HA in a dose-dependent manner. High-MW HA also protects against the damage to articular chondrocytes by oxygen-derived free radicals, which are known to play a role in the pathogenesis of arthritic disorders [ 79 ].
Lastly, in avian embryonic fibroblasts, HA reduced cell damage induced by hydroxyl radicals in a MW- and dose-dependent manner [ 80 ]. The effects of HA on NO, well recognized for its role in inflammation, may be tissue specific. Production of NO from the meniscus and synovium of a rabbit OA model was significantly reduced with HA treatment [ 81 ]. Other experiments showed that HA did not affect NO production from articular cartilage [ 82 , 83 ]. In hepatic cells, fragments of HA increased the expression of the inducible form of NO synthase, while high-MW HA did not have an effect on its expression [ 84 ].
Besides altering the production and activity of inflammatory mediators and proteases, HA can change the behavior of immune cells. Its effects on immune cells are summarized in Table 4.
HA has been shown to reduce the motility of lymphocytes; this observation occurred with physiological fluids i. When the HA in these fluids was digested with hyaluronidase, it no longer inhibited the motility, indicating that the motility inhibition depended on the molecular size and polysaccharide conformation of the molecule [ 25 ].
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