Accumulation Of Hyaluronic Acid Research Articles

Evaluation of Radiation and Ammonium Lactate Effects on Hyaluronic Acid Expression as a Pro-cancerous Factor in Supernatant and Exosome Isolated from Supernatant of Primary Mouse Fibroblast Cell Culture.

Background:Previous studies show that aberrant synthesis of Hyaluronan accelerates tumor growth, angiogenesis, and metastasis. The fibroblasts are probably responsible for most of the hyaluronic acid (HA) accumulation in tumor microenvironment after radiotherapy. Our goal is to investigate and compare radiation and lactate effects on HA levels in supernatant and exosome isolated from supernatant of primary mouse fibroblast cell culture.Methods:Fibroblast cells were prepared from skin of C57BL6 mouse. These cells were divided into three groups (no treatment, cells treated with 10 mM ammonium lactate, and irradiated cells). Then supernatant was harvested from FBS-free culture media after 48 h. Exosomes were purified by differential centrifugation (300 × g for 10 min, 2000 × g for 30 min, 16500 g for 30 min) and were pelleted by ultracentrifugation (150,000 × g for 180 min). Size of exosomes was determined using a Zetasizer. HA concentration measured using a HA ELISA Kit. Data were analyzed using one-way ANOVA.Results:There was a significant increase in HA-coated exosomes isolated from supernatants of irradiated cells compared to untreated cell and cells treated with 10 mM ammonium lactate (P < 0.001). As well, there was a significant increase in the HA concentration in the supernatants of cells treated with 10 mM ammonium lactate relative to untreated cells and irradiated cells (P < 0.05).Conclusions:It seems that routine radiation therapy leads to massive shedding of HA-coated exosomes by normal fibroblast cells and thus exosomes-HA may contribute to tumor promotion and induce of the premetastatic niche.

Correlation of serum hyaluronic acid with diabetic indices in type 2 diabetes mellitus patients with diabetic nephropathy

Introduction: Hyaluronic Acid (HA) is produced by the endothelial smooth muscle cells and adventitial fibroblasts of the arterial wall. In conditions of hyperglycemia, there is an accumulation of HA in blood vessels and can contribute to the diabetic micro- and macrovascular complications. The current study aims to determine the association of serum Hyaluronic Acid levels in Type 2 diabetes mellitus with diabetic nephropathy and its correlation with diabetic indices and renal function test parameters. Materials and Methods: 60 male subjects,30 cases of Type 2 Diabetes Mellitus patients with diabetic nephropathy and 30 non-diabetic healthy subjects as controls. Fasting venous blood samples were collected from cases and controls and analyzed for serum HA by ELISA and HBA1C, FBS, PPBS, urea, and creatinine by Beckmann Coulter Au 480 automated analyser.24 hours urine was collected and analyzed for urinary microalbumin by an immunoturbidimetric method. Statistical analysis was done with SPSS package and p-value Results: Serum HA levels were significantly higher in diabetic patients with nephropathy (756 ng/ml) when compared to the normal control groups (255 ng/ml). Serum HA also showed a significant positive correlation with FBS, PPBS, HbA1C, urea, creatinine and urine microalbumin. Conclusion: Highly elevated serum Hyaluronic Acid levels and its positive correlation with diabetic indices and renal function test parameters in Type 2 Diabetes Mellitus patients with diabetic nephropathy suggests its association with poor blood glucose control and may possibly predict the development of diabetesrelated vascular complications in Type 2 diabetics without any complications. Keywords: Type 2 Diabetes Mellitus, Hyaluronic acid, Glycocalyx.

OROFACIAL GRANULOMAS AFTER INJECTION OF COSMETIC FILLERS: A CASE REPORT

The increasing demand for cosmetic procedures in the orofacial area results in a growing number of complications, including the development of foreign body granulomas. A 55-year-old woman presented with submucosal and subcutaneous nodules that were firm on palpation, which had arisen approximately 30 days earlier in the right buccal mucosa and in the face (cervical, submentonian, and submandibular regions). The diagnostic hypothesis was lymphoma, but after the clinical examination, the patient reported having undergone facial filling procedure 1 year before. Ultrasonography showed nodular images suggestive of reactive granulomas. Preoperative tests were requested, and incisional surgical biopsy was performed. Histologic analysis showed granulomatous reactions associated with the use of hyaluronic acid (accumulation of amorphous basophilic material) and polymethylmethacrylate (refringent material, without dye impregnation). The patient was unaware of the facial filling with polymethylmethacrylate.

Hyaluronic acid is required for palatal shelf movement and its interaction with the tongue during palatal shelf elevation

Palatal shelf elevation is an essential morphogenetic process that results from palatal shelf movement caused by an intrinsic elevating force. The nature of the elevating force remains unclear, but the accumulation of hyaluronic acid (HA) in the extracellular matrix (ECM) of the palatal shelves may play a pivotal role in developing the elevating force. In mammals, HA is synthesized by hyaluronic acid synthases (HAS) that are encoded by three genes (Has1-3). Here, we used the Wnt1-Cre driver to conditionally disrupt hyaluronic acid synthase 2 (Has2) in cranial neural crest cell lineages. All Has2 conditional knockout (cko) mice had cleft palate due to failed shelf elevation during palate development. The HA content was significantly reduced in the craniofacial mesenchyme of Has2 cko mutants. Reduced HA content affected the ECM space and shelf expansion to result in a reduced shelf area and an increased mesenchymal cell density in the palatal shelves of Has2 cko mutants. We examined palatal shelf movement by removal of the tongue and mandible from unfixed E13.5 and early E14.5 embryonic heads. Reduced shelf expansion in Has2 cko mutants altered palatal shelf movement in the medial direction resulting in a larger gap between the palatal shelves than that of littermate controls. We further examined palatal shelf movement in the intact oral cavity by culturing explants containing the maxilla, palate, mandible and tongue (MPMT explants). The palatal shelves elevated alongside morphological changes in the tongue after 24-h culture in MPMT explants of early E14.5 wild type embryos. On the contrary, shelf elevation failed to occur in MPMT explants of age-matched Has2 cko mutants because the tongue obstructs palatal shelf movement, suggesting that reduced shelf expansion could be essential for the palatal shelves to interact with the tongue and overcome tongue obstruction during shelf elevation. Has2 cko mutants also showed micrognathia due to reduced HA content in the mandibular mesenchyme including Meckel’s cartilage. Through 3D imaging and morphometric analysis, we demonstrate that mandibular growth results in a significant increase in the vertical dimension of the common oral-nasal cavity that facilitates palatal shelf movement and its interaction with the tongue during shelf elevation.

Связь между хроническим воспалением и развитием мастоцитомы у шарпеев

This article is devoted to the study of the connection between autoinflammatory disease and the development of a mast cell tumor on the example of Shar-Pei. The HAS2 gene, which is responsible for the synthesis of hyaluronic acid, in Shar-Pei has an increased expression due to which hyaluronic acid accumulates in the dermis, forming breed-defining skin phenotype — thik skin folds. It became known that hyaluronic acid is involved in immune reactions. Under normal conditions, it is in the high molecular weight fraction, but in abundant it begins to fragment into low molecular weight polymers interacting with the membranes of mast cells, as an antigen, due to chemical similarity with the microbial surface. Thus, mast cells and other immunocompetent cells initiate the inflammatory process. Therefore, the breed predisposition of Shar-Pei to the accumulation of hyaluronic acid can cause self-inflammatory diseases in dogs. The link with mastocytoma can be traced because hyaluronic acid also affects the proliferation and terminal differentiation of mast cells, interacting with the CD44 co-receptor of c-kit receptor. The KIT gene is marked by researchers as the gene responsible for the active proliferation of mast cells. There were found mutations in the same gene in dogs with a mastocytoma. Perhaps the appearance of hyaluronic acid in chronic inflammation, as well as in the development of mastocytoma indicate the presence of a connection between both pathological processes.

Accumulation of hyaluronic acid in stromal cells modulates osteoclast formation by regulation of receptor activator of nuclear factor kappa-B ligand expression

Hyaluronic acid (HA) has a pivotal role in bone and cartilage metabolism. In this study, we investigated the effect and underlying mechanisms of HA accumulation on the expression of receptor activator of nuclear factor kappa-B ligand (RANKL) induced by 1α,25(OH)2D3 and dexamethasone in stromal cells, which support osteoclastogenesis. Degradation of HA by hyaluronidase (HA'ase) treatment enhanced the expression of RANKL in ST2 cells stimulated with 1α,25(OH)2D3 and dexamethasone. Down-regulation of hyaluronan synthase 2 (HAS2) expression by siRNA also stimulated RANKL expression induced by 1α,25(OH)2D3 and dexamethasone. Results from a cell co-culture system with bone marrow cell showed that 1α,25(OH)2D3 and dexamethasone-induced RANKL expression in HA'ase treated- and HAS2 siRNA transfected-ST2 cells was down-regulated by treatment of cells with high molecular weight HA. In contrast, transforming growth factor-β1 (TGF-β1), which stimulates HAS2 expression and HA synthesis, down-regulated RANKL expression induced by 1α,25(OH)2D3 and dexamethasone. Interestingly, knockdown of has2 gene enhanced the expression of vitamin D receptor (VDR) and phosphorylation of signal transducers and activator of transcription 3 (STAT3) in ST2 cells stimulated by 1α,25(OH)2D3 and dexamethasone. These results indicate that accumulation of HA in bone marrow cells may affect RANKL-mediated osteoclast-supporting activity via regulation of VDR and STAT3 signaling pathways.

Observation using thermography of post-operative reaction after fascial manipulation®.

Fascia Manipulation® is one of the methods focusing on the deep fascia. The assumption is that fascial manipulation is carried out on precisely determined points - coordination centres (cc), and on a limited area so as the friction occurring during manipulation would cause a local rise in temperature due to the inflammatory reaction. Rise in temperature influences modification in consistency of elementary matter in the manipulated area, and by the same token causing a decrease in the negative effects of fascia densification which stems from accumulation of hyaluronic acid. The purpose of the research is to prove the thesis that fascial manipulation causes local rise in temperature due to inflammatory reaction. For the research, 25 individuals with densification in lower limb area were qualified. They were exposed to a single, 3-minute facial manipulation®. By means of a thermal-imaging camera, changes in the temperature of the body in the examined area were evaluated. The body's temperature evaluation was carried out 8 times: before the treatment, 5 minutes after the treatment, and, next, 6, 12, 18, 24, 36, 48 hours after the treatment. The average surface temperature of the treated area before mobilization was 33.4°C. A statistically relevant increase in temperature was already observed 5 minutes after the treatment (increase of 0.5°C; p<0.001). However, the highest temperature was observed 24 hours after mobilization (increase of 2.4°C). The difference between the first and 7 other measurements was statistically relevant (p<0.001). The statistically relevant increase in temperature under the influence of fascial manipulation® in the treatment area can confirm the occurrence of inflammatory reaction.

Human hyaluronic acid synthase-1 promotes malignant transformation via epithelial-to-mesenchymal transition, micronucleation and centrosome abnormalities

BackgroundHuman hyaluronic acid (HA) molecules are synthesized by three membrane spanning Hyaluronic Acid Synthases (HAS1, HAS2 and HAS3). Of the three, HAS1 is found to be localized more into the cytoplasmic space where it synthesizes intracellular HA. HA is a ubiquitous glycosaminoglycan, mainly present in the extracellular matrix (ECM) and on the cell surface, but are also detected intracellularly. Accumulation of HA in cancer cells, the cancer-surrounding stroma, and ECM is generally considered an independent prognostic factors for patients. Higher HA production also correlates with higher tumor grade and more genetic heterogeneity in multiple cancer types which is known to contribute to drug resistance and results in treatment failure. Tumor heterogeneity and intra-tumor clonal diversity are major challenges for diagnosis and treatment. Identification of the driver pathway(s) that initiate genomic instability, tumor heterogeneity and subsequent phenotypic/clinical manifestations, are fundamental for the diagnosis and treatment of cancer. Thus far, no evidence was shown to correlate intracellular HA status (produced by HAS1) and the generation of genetic diversity in tumors.MethodsWe tested different cell lines engineered to induce HAS1 expression. We measured the epithelial traits, centrosomal abnormalities, micronucleation and polynucleation of those HAS1-expressing cells. We performed real-time PCR, 3D cell culture assay, confocal microscopy, immunoblots and HA-capture methods.ResultsOur results demonstrate that overexpression of HAS1 induces loss of epithelial traits, increases centrosomal abnormalities, micronucleation and polynucleation, which together indicate manifestation of malignant transformation, intratumoral genetic heterogeneity, and possibly create suitable niche for cancer stem cells generation.ConclusionsThe intracellular HA produced by HAS1 can aggravate genomic instability and intratumor heterogeneity, pointing to a fundamental role of intracellular HA in cancer initiation and progression.

Modulating Wnt Signaling Rescues Palate Morphogenesis in Pax9 Mutant Mice

Cleft palate is a common birth defect caused by disruption of palatogenesis during embryonic development. Although mutations disrupting components of the Wnt signaling pathway have been associated with cleft lip and palate in humans and mice, the mechanisms involving canonical Wnt signaling and its regulation in secondary palate development are not well understood. Here, we report that canonical Wnt signaling plays an important role in Pax9-mediated regulation of secondary palate development. We found that cleft palate pathogenesis in Pax9-deficient embryos is accompanied by significantly reduced expression of Axin2, an endogenous target of canonical Wnt signaling, in the developing palatal mesenchyme, particularly in the posterior regions of the palatal shelves. We found that expression of Dkk2, encoding a secreted Wnt antagonist, is significantly increased whereas the levels of active β-catenin protein, the essential transcriptional coactivator of canonical Wnt signaling, is significantly decreased in the posterior regions of the palatal shelves in embryonic day 13.5 Pax9-deficent embryos in comparison with control littermates. We show that small molecule–mediated inhibition of Dickkopf (DKK) activity in utero during palatal shelf morphogenesis partly rescued secondary palate development in Pax9-deficient embryos. Moreover, we found that genetic inactivation of Wise, which is expressed in the developing palatal shelves and encodes another secreted antagonist of canonical Wnt signaling, also rescued palate morphogenesis in Pax9-deficient mice. Furthermore, whereas Pax9del/del embryos exhibit defects in palatal shelf elevation/reorientation and significant reduction in accumulation of hyaluronic acid—a high molecular extracellular matrix glycosaminoglycan implicated in playing an important role in palatal shelf elevation—80% of Pax9del/del;Wise-/- double-mutant mouse embryos exhibit rescued palatal shelf elevation/reorientation, accompanied by restored hyaluronic acid accumulation in the palatal mesenchyme. Together, these data identify a crucial role for canonical Wnt signaling in acting downstream of Pax9 to regulate palate morphogenesis.

Topical stabilized retinol treatment induces the expression of HAS genes and HA production in human skin in vitro and in vivo

Skin Aging manifests primarily with wrinkles, dyspigmentations, texture changes, and loss of elasticity. During the skin aging process, there is a loss of moisture and elasticity in skin resulting in loss of firmness finally leading to skin sagging. The key molecule involved in skin moisture is hyaluronic acid (HA), which has a significant water-binding capacity. HA levels in skin decline with age resulting in decrease in skin moisture, which may contribute to loss of firmness. Clinical trials have shown that topically applied ROL effectively reduces wrinkles and helps retain youthful appearance. In the current study, ROL was shown to induce HA production and stimulates the gene expression of all three forms of hyaluronic acid synthases (HAS) in normal human epidermal keratinocytes monolayer cultures. Moreover, in human skin equivalent tissues and in human skin explants, topical treatment of tissues with a stabilized-ROL formulation significantly induced the gene expression of HAS mRNA concomitant with an increased HA production. Finally, in a vehicle-controlled human clinical study, histochemical analysis confirmed increased HA accumulation in the epidermis in ROL-treated human skin as compared to vehicle. These results show that ROL increases skin expression of HA, a significant contributing factor responsible for wrinkle formation and skin moisture, which decrease during aging. Taken together with the activity to increase collagen, elastin, and cell proliferation, these studies establish that retinol provides multi-functional activity for photodamaged skin.

Radionuclide Esophageal Transit Scintigraphy in Primary Hypothyroidism.

Background/AimsEsophageal dysmotility is associated with gastrointestinal dysmotility in various systemic and neuroregulatory disorders. Hypothyroidism has been reported to be associated with impaired motor function in esophagus due to accumulation of glycosaminoglycan hyaluronic acid in its soft tissues, leading to changes in various contraction and relaxation parameters of esophagus, particularly in the lower esophageal sphincter. In this study we evaluated esophageal transit times in patients of primary hypothyroidism using the technique of radionuclide esophageal transit scintigraphy.MethodsThirty-one patients of primary hypothyroidism and 15 euthyroid healthy controls were evaluated for esophageal transit time using 15–20 MBq of Technetium-99m sulfur colloid diluted in 10–15 mL of drinking water. Time activity curve was generated for each study and esophageal transit time was calculated as time taken for clearance of 90% radioactive bolus from the region of interest encompassing the esophagus. Esophageal transit time of more than 10 seconds was considered as prolonged.ResultsPatients of primary hypothyroidism had a significantly increased mean esophageal transit time of 19.35 ± 20.02 seconds in comparison to the mean time of 8.25 ± 1.71 seconds in healthy controls (P < 0.05). Esophageal transit time improved and in some patients even normalized after treatment with thyroxine. A positive correlation (r = 0.39, P < 0.05) albeit weak existed between the serum thyroid stimulating hormone and the observed esophageal transit time.ConclusionsA significant number of patients with primary hypothyroidism may have subclinical esophageal dysmotility with prolonged esophageal transit time which can be reversible by thyroxine treatment. Prolonged esophageal transit time in primary hypothyroidism may correlate with serum thyroid stimulating hormone levels.

Expression and purification of RHC–EGFP fusion protein and its application in hyaluronic acid assay

ABSTRACTHyaluronan is a widely distributed glycosaminoglycan which has multiple functions. Hyaluronic acid (HA) accumulation has been reported in many human diseases. Understanding the role of hyaluronan and its binding proteins in the pathobiology of disease will facilitate the development of novel therapeutics for many critical diseases. Current techniques described for the analysis of HA are mainly for HA quantification in solutions, not for the direct detection of HA in tissues or on cell surfaces. In our study, a fusion protein, named C-terminal domain of RHAMM–enhanced green fluorescence protein (RHC–EGFP), combined the HA-binding domain, C-terminal of receptor for hyaluronan-mediated motility, with EGFP, a widely used enhanced green fluorescence protein, was expressed and purified from Escherichia coli with high purity. Based on the sensitivity and convenience of fluorescence detection, methods for direct assay of HA in solutions, on cell surface or in tissues were established using RHC–EGFP. The binding specificity was also confirmed by competitive binding experiment and hyaluronidase degradation experiment. Our results provide an alternative choice for the specific and convenient assay of HA in various samples, and maybe helpful for further understanding of the fundamental and comprehensive functions of HA.

Controlled Release of Hepatocyte Growth Factor from MPEG-b-(PCL-ran-PLLA) Diblock Copolymer for Improved Vocal Fold Regeneration.

An in situ-forming gel system comprised of diblock copolymer formed from polyethylene glycol (PEG) and polycaprolactone (PCL) {MPEG-b-(PCL-ran-PLLA)} could be used in controlled drug delivery for tissue remodeling. The purpose of this study is to demonstrate favorable vocal folds (VF) regeneration by using MPEG-b-(PCL-ran-PLLA) diblock copolymers (C97L3; CL/LA ratio 97:3) incorporating hepatocyte growth factor (HGF). Gradual release of HGF from C97L3 is detected and biochemical properties of released HGF are maintained. A scar is made with microscissors on both VFs in 32 rabbits, followed by injection of HGF-only, C97L3-only, or HGF-C97L3 composite gel in the left side VF, while the right side VF is left untreated. In vivo fluorescence live imaging system demonstrates that C97L3 enables the sustained release of injected HGF in the scarred VF for 12 weeks. The histological analysis shows increased glycosaminoglycan including hyaluronic acid accumulation and decreased collagen deposition. Videokymographic analysis shows more favorable vibrations of HGF-C97L3 treated VF mucosa, compared to other treatment groups. In conclusion, the controlled HGF release helps to regulate extracellular matrix synthesis, and leads to the eventual functional improvement of the scarred VF.

Can CD44 Be a Mediator of Cell Destruction? The Challenge of Type 1 Diabetes.

CD44 is a multi-functional receptor with multiple of isoforms engaged in modulation of cell trafficking and transmission of apoptotic signals. We have previously shown that injection of anti-CD44 antibody into NOD mice induced resistance to type 1 diabetes (T1D). In this communication we describe our efforts to understand the mechanism underlying this effect. We found that CD44-deficient NOD mice develop stronger resistance to T1D than wild-type littermates. This effect is not explained by the involvement of CD44 in cell migration, because CD44-deficient inflammatory cells surprisingly had greater invasive potential than the corresponding wild type cells, probably owing to molecular redundancy. We have previously reported and we show here again that CD44 expression and hyaluronic acid (HA, the principal ligand for CD44) accumulation are detected in pancreatic islets of diabetic NOD mice, but not of non-diabetic DBA/1 mice. Expression of CD44 on insulin-secreting β cells renders them susceptible to the autoimmune attack, and is associated with a diminution in β-cells function (e.g., less insulin production and/or insulin secretion) and possibly also with an enhanced apoptosis rate. The diabetes-supportive effect of CD44 expression on β cells was assessed by the TUNEL assay and further strengthened by functional assays exhibiting increased nitric oxide release, reduced insulin secretion after glucose stimulation and decreased insulin content in β cells. All these parameters could not be detected in CD44-deficient islets. We further suggest that HA-binding to CD44-expressing β cells is implicated in β-cell demise. Altogether, these data agree with the concept that CD44 is a receptor capable of modulating cell fate. This finding is important for other pathologies (e.g., cancer, neurodegenerative diseases) in which CD44 and HA appear to be implicated.

In vivo role of Candida albicans β-hexosaminidase (HEX1) in carbon scavenging.

The capability to utilize of N-acetylglucosamine (GlcNAc) as a carbon source is an important virulence attribute of Candida albicans. But there is a lack of information about the in vivo source of GlcNAc for the pathogen within the host environment. Here, we have characterized the GlcNAc-inducible β-hexosaminidase gene (HEX1) of C. albicans showing a role in carbon scavenging. In contrast to earlier studies, we have reported HEX1 to be a nonessential gene as shown by homozygous trisomy test. Virulence study in the systemic mouse murine model showed that Δhex1 strain is significantly less virulent in comparison to the wild-type strain. Moreover, Δhex1 strain also showed a higher susceptibility to peritoneal macrophages. In an attempt to determine possible substrates of Hex1, hyaluronic acid (HA) was treated with purified Hex1 enzyme. A significant release of GlcNAc was observed by gas chromatography-mass spectrometry analysis analysis suggesting HA degradation. Interestingly, immunohistochemistry analysis showed significant accumulation of HA in the mice kidney infected with the wild-type strain of C. albicans. Northern blot analysis showed that C. albicans HEX1 is expressed during mice renal colonization. Thus, C. albicans can obtain GlcNAc during organ colonization by secreting Hex1 via degradation of host HA.

Hyaluronic acid regulates a key redox control factor Nrf2 via phosphorylation of Akt in bovine articular chondrocytes

One important pharmacological function of hyaluronic acid (HA) in chondrocytes is reduction of cellular superoxide generation and accumulation. Here we demonstrated a relationship between HA supplementation and accumulation of Nuclear factor-erythroid-2-related factor 2 (Nrf2), which is a master transcription factor in cellular redox reactions, in cultured chondrocytes derived from bovine joint cartilage. In HA-treated chondrocytes, expression of Nrf2 and its downstream genes was upregulated. In HA-treated chondrocytes, Akt was phosphorylated, and inhibition of Akt activity or suppression of HA receptors CD44 and/or RHAMM with siRNAs prevented HA-mediated Nrf2 accumulation. Furthermore, Nrf2 siRNA inhibited the HA effect on antioxidant enzymes. These results show that HA might contribute to ROS reduction through Nrf2 regulation by activating Akt. Our study suggests a new mechanism for extracellular matrix (ECM)-mediated redox systems in chondrocytes.

Small intestine submucosa and mesenchymal stem cells composite gel for scarless vocal fold regeneration

The purpose of this study is to demonstrate scarless vocal fold (VF) regeneration by using a composite gel composed of small intestine submucosa (SIS) and mesenchymal stem cells (MSCs). A scar was made with an electrocoagulator on both VFs in 24 rabbits, followed by injection of either MSCs, SIS, or MSCs-SIS composite gel in the right side VF, while the left side VF was left untreated. VF scars were evaluated with in vivo fluorescence live imaging system (IFLIS), endoscopy, histology, and videokymography (VKG) after eight weeks. IFLIS demonstrated that SIS enabled the MSCs to survive and be engrafted in the VF. The histological analysis showed increased hyaluronic acid accumulation and controlled collagen deposition by MSCs-SIS composite gel. VKG analysis showed more favorable vibrations of MSCs-SIS injected VF, compared to other treatment group. In conclusion, the injectable SIS supplied a niche for the MSCs to stably settle down in scarred VFs and helped to regulate ECM synthesis. The ECM remodeling underwent by the surviving MSCs eventually led to the functional improvement of the VF. The results of the present investigation suggest that SIS-MSCs composite gel is a plausible biomaterial for prolonged survival of MSCs in VFs and promotes scarless VF healing.

PReS-FINAL-2031: Hyaluronic acid is a marker of active arthritis, but not systemic inflammation in systemic juvenile idiopathic arthritis

Systemic juvenile idiopathic arthritis (JIA) is a subtype of childhood arthritis associated with significant systemic inflammation as well as arthritis. Hyaluronic acid as a constituent of connective tissue has previously been described as a marker for arthritis in JIA in an Asian population. Mutations in hyaluronic acid synthase 2 leading to accumulation of hyaluronic acid have been found to be associated with a periodic fever syndrome in Shar-Pei dogs. Hyaluronic acid has therefore been suspected as a risk factor for systemic inflammation in humans.

SAT0433 Hyaluronic Acid is a Marker of Active Arthritis, but not Systemic Inflammation in Systemic Juvenile Idiopathic Arthritis

BackgroundSystemic juvenile idiopathic arthritis (JIA) is a subtype of childhood arthritis associated with significant systemic inflammation as well as arthritis. Hyaluronic acid as a constituent of connective tissue has previously...

Altered expression of hyaluronan synthase and hyaluronidase mRNA may affect hyaluronic acid distribution in keloid disease compared with normal skin

Keloid disease (KD) is a fibroproliferative disorder characterised partly by an altered extracellular matrix (ECM) profile. In fetal scarring, hyaluronic acid (HA) expression is increased, but is reduced in KD tissue compared with normal skin (NS). The expression of Hyaluronan Synthase (HAS) and hyaluronidase (HYAL) in KD and NS tissue were investigated for the first time using a range of techniques. Hyaluronan synthase and HYAL mRNA expression were significantly increased in NS tissue compared with KD tissue (P < 0.05). Immunohistological analysis of tissue indicated an accumulation of HAS and HYAL protein expression in KD compared with NS due to the thicker epidermis. No differences were observed in mRNA or protein expression in KD and NS fibroblasts. Reduced expression of HAS and HYAL may alter HA synthesis, degradation and accumulation in KD. Better understanding of the role of HA in KD may lead to novel therapeutic approaches to address the resulting ECM imbalance.