Promote Fibroblast Growth Research Articles

Glucosamine Enhancement of Learning and Memory Functions by Promoting Fibroblast Growth Factor 21 Production.

Fibroblast growth factor 21 (FGF21) plays a crucial role in metabolism and brain function. Glucosamine (GLN) has been recognized for its diverse beneficial effects. This study aimed to elucidate the modulation of FGF21 production by GLN and its impact on learning and memory functions. Using both in vivo and in vitro models, we investigated the effects of GLN on mice fed with a normal diet or high-fat diet and on mouse HT22 hippocampal cells, STHdhQ7/Q7 striatal cells, and rat primary cortical neurons challenged with GLN. Our results indicated that GLN promotes learning and memory functions in mice and upregulates FGF21 expression in the hippocampus, cortex, and striatum, as well as in HT22 cells, STHdhQ7/Q7 cells, and cortical neurons. In animals receiving GLN together with an FGF21 receptor FGFR1 inhibitor (PD173074), the GLN-enhanced learning and memory functions and induction of FGF21 production in the hippocampus were significantly attenuated. While exploring the underlying molecular mechanisms, the potential involvement of NF-κB, Akt, p38, JNK, PKA, and PPARα in HT22 and NF-κB, Akt, p38, and PPARα in STHdhQ7/Q7 were noted; GLN was able to mediate the activation of p65, Akt, p38, and CREB in HT22 and p65, Akt, and p38 in STHdhQ7/Q7 cells. Our accumulated findings suggest that GLN may increase learning and memory functions by inducing FGF21 production in the brain. This induction appears to be mediated, at least in part, through GLN's activation of the NF-κB, Akt, p38, and PKA/CREB pathways.

Surface modification of a commercial bone plate (Ti6Al4V) implant for improved antibacterial and cytocompatibility via thermal dewetting of a silver thin film

The high demand for bone grafts has motivated the development of implants with excellent osteogenic activity, whereas the risk of implant-associated infection, particularly given the rise of antimicrobial resistance, has compelled the development of implants with innovative antimicrobial strategies in which a small amount of bactericidal agent can effectively kill a wide range of bacteria. To induce antibacterial property, the surface of Grade-5 bone plate titanium implants used in clinical applications was modified using direct current (DC) sputter coating followed by thermal annealing. The 15 nm silver film-coated implants were thermally annealed in the furnace for 15 min at 750 °C. The modified implant surface’s antibacterial efficacy against Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), Salmonella typhi, and Methicillin-resistant staphylococcus aureus bacteria has been assessed using a colony-forming assay. On the modified implant surface, the growth of E. coli and S. aureus bacteria is reduced by 99.72%, while highly drug-resistant bacteria are inhibited by 96.59%. The MTT assay was used to assess the cytotoxicity of the modified bone-implant surface against NIH3T3 mouse fibroblast cells. The modified bone-implant surface promoted fibroblast growth and demonstrated good cytocompatibility. Furthermore, the mechanical properties of the implant were not harmed by this novel surface modification method. This method is simple and provides new insight into surface modification of commercial metallic implants to have effective antibacterial properties against various classes of bacteria.

Facile synthesis of nanoparticles-stacked Co3O4 nanoflakes with catalase-like activity for accelerating wound healing.

Delayed wound healing caused by excessive reactive oxygen species (ROS) remains a considerable challenge. In recent years, metal oxide nanozymes have gained significant attention in biomedical research. However, a comprehensive investigation of Co3O4-based nanozymes for enhancing wound healing and tissue regeneration is lacking. This study focuses on developing a facile synthesis method to produce high-stability and cost-effective Co3O4 nanoflakes (NFs) with promising catalase (CAT)-like activity to regulate the oxidative microenvironment and accelerate wound healing. The closely arranged Co3O4 nanoparticles (NPs) within the NFs structure result in a significantly larger surface area, thereby amplifying the enzymatic activity compared to commercially available Co3O4 NPs. Under physiological conditions, it was observed that Co3O4 NFs efficiently break down hydrogen peroxide (H2O2) without generating harmful radicals (·OH). Moreover, they exhibit excellent compatibility with various cells involved in wound healing, promoting fibroblast growth and protecting cells from oxidative stress. In a rat model, Co3O4 NFs facilitate both the hemostatic and proliferative phases of wound healing, consequently accelerating the process. Overall, the promising results of Co3O4 NFs highlight their potential in promoting wound healing and tissue regeneration.

GDF15 is required for cold-induced thermogenesis and contributes to improved systemic metabolic health following loss of OPA1 in brown adipocytes.

We previously reported that mice lacking the protein optic atrophy 1 (OPA1 BKO) in brown adipose tissue (BAT) display induction of the activating transcription factor 4 (ATF4), which promotes fibroblast growth factor 21 (FGF21) secretion as a batokine. FGF21 increases metabolic rates under baseline conditions but is dispensable for the resistance to diet-induced obesity (DIO) reported in OPA1 BKO mice (Pereira et al., 2021). To determine alternative mediators of this phenotype, we performed transcriptome analysis, which revealed increased levels of growth differentiation factor 15 (GDF15), along with increased protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) levels in BAT. To investigate whether ATF4 induction was mediated by PERK and evaluate the contribution of GDF15 to the resistance to DIO, we selectively deleted PERK or GDF15 in OPA1 BKO mice. Mice with reduced OPA1 and PERK levels in BAT had preserved ISR activation. Importantly, simultaneous deletion of OPA1 and GDF15 partially reversed the resistance to DIO and abrogated the improvements in glucose tolerance. Furthermore, GDF15 was required to improve cold-induced thermogenesis in OPA1 BKO mice. Taken together, our data indicate that PERK is dispensable to induce the ISR, but GDF15 contributes to the resistance to DIO, and is required for glucose homeostasis and thermoregulation in OPA1 BKO mice by increasing energy expenditure.

Antibacterial, injectable, and adhesive hydrogel promotes skin healing.

With the development of material science, hydrogels with antibacterial and wound healing properties are becoming common. However, injectable hydrogels with simple synthetic methods, low cost, inherent antibacterial properties, and inherent promoting fibroblast growth are rare. In this paper, a novel injectable hydrogel wound dressing based on carboxymethyl chitosan (CMCS) and polyethylenimine (PEI) was discovered and constructed. Since CMCS is rich in -OH and -COOH and PEI is rich in -NH2, the two can interact through strong hydrogen bonds, and it is theoretically feasible to form a gel. By changing their ratio, a series of hydrogels can be obtained by stirring and mixing with 5wt% CMCS aqueous solution and 5wt% PEI aqueous solution at volume ratios of 7:3, 5:5, and 3:7. Characterized by morphology, swelling rate, adhesion, rheological properties, antibacterial properties, in vitro biocompatibility, and in vivo animal experiments, the hydrogel has good injectability, biocompatibility, antibacterial (Staphylococcus aureus: 56.7 × 107CFU/mL in the blank group and 2.5 × 107CFU/mL in the 5/5 CPH group; Escherichia coli: 66.0 × 107CFU/mL in the blank group and 8.5 × 107CFU/mL in the 5/5 CPH group), and certain adhesion (0.71kPa in the 5/5 CPH group) properties which can promote wound healing (wound healing reached 98.02% within 14days in the 5/5 CPH group) and repair of cells with broad application prospects.

FGFBP1-mediated crosstalk between fibroblasts and pancreatic cancer cells via FGF22/FGFR2 promotes invasion and metastasis of pancreatic cancer.

Fibroblast growth factor-binding protein 1 (FGFBP1) promotes fibroblast growth factor (FGF) activity by releasing FGFs from extracellular matrix storage. We previously reported that the tumor suppressor F-box and WD repeat domain-containing 7 suppresses FGFBP1 by reducing expression of c-Myc, which inhibits the proliferation and migration of pancreatic cancer cells. However, the potential mechanism by which FGFBP1 facilitates pancreatic ductal adenocarcinoma (PDAC) remains unexplored. In this study, we focused on the function of FGFBP1 in the interplay between cancer-associated fibroblasts (CAFs) and pancreatic cancer cells (PCCs). Decreased FGF22 expression was detected in CAFs co-cultured with PCCs with FGFBP1 abrogation, which was verified in the cell culture medium by enzyme-linked immunosorbent assay. Active cytokine FGF22 significantly facilitated the migration and invasion of PANC-1 and Mia PaCa-2 cells. The number of penetrating PCCs cocultured with CAFs with FGF22 abrogation was significantly less than that of the control group. Interestingly, higher expressions of FGF22 and fibroblast growth factor receptor 2 (FGFR2) were associated with worse prognosis of patients with PDAC and FGFR2, an independent prognostic marker of PDAC. The PANC-1 and Mia PaCa-2 cells with silenced FGFR2 showed weaker invasion and metastasis, even if these cells were simultaneously treated with cytokine FGF22. These results revealed that FGFBP1-mediated interaction between CAFs and PCCs via FGF22/FGFR2 facilitates the migration and invasion of PCCs. FGFR2 could act as a prognostic marker for patients with PDAC.

Prussian blue and collagen loaded chitosan nanofibers with NIR-controlled NO release and photothermal activities for wound healing

1 Prussian blue and collagen loaded chitosan electrospun nanofibers were fabricated. 2 The chitosan nanofibers possess NIR controlled NO release and PTT activities. 3 The nanofibers displayed synergetic antibacterial against E. coli and S. aureus . 4 The nanofibers promoted collagen deposition, cell growth, and epithelialization. 5 The nanofibers provide sufficient biosafety for wound healing. Nitric oxide (NO) has emerged as a potential wound therapeutic agent due to its pivotal role in the wound healing processes. Nevertheless, NO-based therapy for clinical applications is still restricted due to its gaseous state and short half-life. Here we exploited a wound dressing by incorporating sodium nitroprusside doped prussian blue nanoparticals and Type I collagen into the chitosan/poly(vinyl alcohol) nanofibers through the electrospinning method. This hybrid nanofibrous scaffold possess the excellent abilities of NIR controlled NO release, photothermal therapy, and imitation of extra-cellular matrix-like architecture. These synergistic effects could enhance their anti-bactericidal effects in vitro and furthermore accelerate wound healing in vivo when compared to control groups. Histological analysis demonstrated the scaffold could promote fibroblast growth and accelerate epithelialization. Moreover, no apparent histological toxicology and negligible damage to major organs were observed, which provided sufficient biosafety for in vivo application. These data indicate the fabricated hybrid nanofibrous scaffold could be used as an ideal candidate for accelerating wound healing and treating chronic wounds.

Rapid and Superior Bacteria Killing of Carbon Quantum Dots/ZnO Decorated Injectable Folic Acid-Conjugated PDA Hydrogel through Dual-Light Triggered ROS and Membrane Permeability.

One of the most difficult challenges in the biomedical field is bacterial infection, which causes tremendous harm to human health. In this work, an injectable hydrogel is synthesized through rapid assembly of dopamine (DA) and folic acid (FA) cross-linked by transition metal ions (TMIs, i.e., Zn2+ ), which was named as DFT-hydrogel. Both the two carboxyl groups in the FA molecule and catechol in polydopamine (PDA) easily chelates Zn2+ to form metal-ligand coordination, thereby allowing this injectable hydrogel to match the shapes of wounds. In addition, PDA in the hydrogel coated around carbon quantum dot-decorated ZnO (C/ZnO) nanoparticles (NPs) to rapidly generate reactive oxygen species (ROS) and heat under illumination with 660 and 808 nm light, endows this hybrid hydrogel with great antibacterial efficacy against Staphylococcus aureus (S. aureus, typical Gram-positive bacteria) and Escherichia coli (E. coli, typical Gram-negative bacteria). The antibacterial efficacy of the prepared DFT-C/ZnO-hydrogel against S. aureus and E. coli under dual-light irradiation is 99.9%. Importantly, the hydrogels release zinc ions over 12 days, resulting in a sustained antimicrobial effect and promoted fibroblast growth. Thus, this hybrid hydrogel exhibits great potential for the reconstruction of bacteria-infected tissues, especially exposed wounds.

MiR-6836-3p promotes proliferation of hypertrophic scar fibroblasts by targeting CTGF.

To explore the role of micro ribonucleic acid (miR)-6836-3p in regulating hypertrophic scar (HS) and its potential mechanism. The level of miR-6836-3p in HS or normal skin was determined by Real-Time Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Cell counting kit-8 (CCK8) and flow cytometry were applied to explore the effect of miR-98 on the growth and apoptosis of HS fibroblasts (HSFBs). Luciferase assay was employed to acknowledge whether connective tissue growth factor (CTGF) is a target of miR-6836-3p. Western blotting was used to detect the protein expression of CTGF after transfection with miR-6836-3p mimic or inhibitor. MiR-6836-3p expression was much higher in HS than that in normal skin. MiR-6836-3p mimic promoted fibroblast growth, and CTGF was confirmed to be a direct target of miR-6836-3p. The results of Western blotting clarified that miR-6836-3p mimic raised the level of CTGF, and its expression was positively correlated with that of CTGF. MiR-6836-3p promoted the development of HS by increasing the expression of CTGF. MiR-6836-3p may be a potential novel molecular target for the treatment of HS.

Albumin downregulates Klotho in tubular cells.

Kidney tubular cells are the main sources of Klotho, a protein with phosphaturic action. Genetic Klotho deficiency causes premature cardiovascular aging in mice. Human chronic kidney disease (CKD) is characterized by acquired Klotho deficiency. Despite the lack of uremic toxin accumulation, Category G1 CKD [(normal glomerular filtration rate (GFR)] is already associated with decreased Klotho and with premature cardiovascular aging. We have explored whether albuminuria, a criterion to diagnose CKD when GFR is normal, may directly decrease Klotho expression in human CKD, preclinical models and cultured tubular cells. In a CKD cohort, albuminuria correlated with serum phosphate after adjustment for GFR, age and sex. In this regard, urinary Klotho was decreased in patients with pathological albuminuria but preserved GFR. Proteinuria induced in rats by puromycin aminonucleoside and in mice by albumin overload was associated with interstitial inflammation and reduced total kidney Klotho messenger ribonucleic acid (mRNA) expression. Western blot disclosed reduced kidney Klotho protein in proteinuric rats and mice and immunohistochemistry localized the reduced kidney Klotho expression to tubular cells in proteinuric animals. In cultured murine and human tubular cells, albumin directly decreased Klotho mRNA and protein expression. This was inhibited by trichostatin A, an inhibitor of histone deacetylases, but unlike cytokine-induced Klotho downregulation, not by inhibitors of nuclear factor kappa-light-chain-enhancer of activated B cells. In conclusion, albumin directly decreases Klotho expression in cultured tubular cells. This may explain, or at least contribute to, the decrease in Klotho and promote fibroblast growth factor 23 resistance in early CKD categories, as observed in preclinical and clinical proteinuric kidney disease.

A novel wound dressing based on a Konjac glucomannan/silver nanoparticle composite sponge effectively kills bacteria and accelerates wound healing

A novel Konjac glucomannan/silver nanoparticle (KGM/AgNP) composite sponge was successfully prepared via a simple 2-step method for biomedical applications as wound-healing materials. First, AgNPs were prepared with green deoxidizer egg white. Then, KGM powder was added to the AgNP solution and stirred vigorously, and the composite sponge was obtained by freeze-drying. The KGM/AgNP composite sponge showed excellent water absorption and water retention, and considerable mechanical properties. KGM/AgNP composite sponges displayed good antibacterial activity against test microorganisms. In vitro cytocompatibility testing showed that L929 cells could survive well in the presence of KGM/AgNPs, indicating that KGM/AgNPs have good cytocompatibility. Animal models showed that the KGM/AgNP composite sponges effectively accelerated wound healing, and histological findings showed that they promoted fibroblast growth and accelerated epithelialization. The experimental results showed that KGM/AgNP composite sponges have great potential in promoting wound healing.

Increased Levels of sRAGE in Diabetic CKD-G5D Patients: A Potential Protective Mechanism against AGE-Related Upregulation of Fibroblast Growth Factor 23 and Inflammation.

Advanced glycation end products (AGEs) may induce cardiac remodeling in kidney disease by promoting fibroblast growth factor 23 (FGF-23) expression. Since AGEs are increased in diabetes mellitus (DM), our first aim was to evaluate the existence of any potential association between AGEs, FGF-23, inflammation, and increased cardiovascular risk in DM patients on dialysis (CKD-G5D). Secondarily, we explored the potential role of the soluble receptor for AGEs (sRAGE) as a marker of heart failure. Levels of glycated albumin (GA), sRAGE, c-terminal FGF-23 (cFGF-23), brain natriuretic peptide (BNP), and inflammatory mediators were compared between DM and non-DM CKD-G5D patients. The levels of sRAGE, cFGF-23, BNP, and proinflammatory markers were over the ranges of normality in both DM and non-DM groups. Only GA and sRAGE levels were increased in DM compared to non-DM patients. Plasma levels of sRAGE and CRP were the only independent predictors of BNP concentration. In conclusion, in DM CKD-G5D patients, sRAGE appeared to be a marker of cardiac remodeling. Indeed, its increase could be a potential protective mechanism against the increased risk of cardiovascular complications related to AGEs and inflammation. The causal relationship between sRAGE and cardiovascular risk in these patients needs to be further confirmed by mechanistic studies.

Nanoparticles Containing Peppermint Oil, Cinnamon Flavor Disrupt Biofilms

When encapsulated in silica nanoparticles, peppermint oil and cinnamaldehyde, which gives cinnamon its characteristic flavor, penetrate biofilms and potently kill drug-resistant pathogens within them, according to Vincent Rotello at the University of Massachusetts, Amherst, and his collaborators. These nanocapsules also promote fibroblast growth, which helps wounds to heal, they say, leading them to call these flavor-loaded nanoparticles a “promising natural disinfectant and wound cleanser.” Details appeared 17 June 2015 in ACS Nano (doi:10.1021/acsnano.5b01696).

The effect of oral collagen peptide supplementation on skin moisture and the dermal collagen network: evidence from an ex vivo model and randomized, placebo-controlled clinical trials.

Skin dryness and an accelerated fragmentation of the collagen network in the dermis are hallmarks of skin aging. Nutrition is a key factor influencing skin health and consequently its appearance. A wide range of dietary supplements is offered to improve skin health. Collagen peptides are used as a bioactive ingredient in nutricosmetic products and have been shown in preclinical studies to improve skin barrier function, to induce the synthesis of collagen and hyaluronic acid, and to promote fibroblast growth and migration. Our aim was to investigate the effect of oral supplementation with specific collagen peptides on skin hydration and the dermal collagen network in a clinical setting. Two placebo-controlled clinical trials were run to assess the effect of a daily oral supplementation with collagen peptides on skin hydration by corneometry, on collagen density by high-resolution ultrasound and on collagen fragmentation by reflectance confocal microscopy. Human skin explants were used to study extracellular matrix components in the presence of collagen peptides ex vivo. Oral collagen peptide supplementation significantly increased skin hydration after 8 weeks of intake. The collagen density in the dermis significantly increased and the fragmentation of the dermal collagen network significantly decreased already after 4 weeks of supplementation. Both effects persisted after 12 weeks. Ex vivo experiments demonstrated that collagen peptides induce collagen as well as glycosaminoglycan production, offering a mechanistic explanation for the observed clinical effects. The oral supplementation with collagen peptides is efficacious to improve hallmarks of skin aging.

α-tocopherol decreases interleukin-1β and -6 and increases human β-defensin-1 and -2 secretion in human gingival fibroblasts stimulated with Porphyromonas gingivalis lipopolysaccharide.

Periodontitis, a disease associated with chronic inflammation, results in significant destruction of periodontal tissues. Uncontrolled, periodontal disease negatively affects general patient health. We sought to evaluate the effect of α-tocopherol on gingival fibroblast behavior following exposure to Porphyromonas gingivalis lipopolysaccharide (LPS). Primary human gingival fibroblasts were cultured for 24 and 48h with α-tocopherol at various concentrations (0, 50, 100 and 200μm) in the presence or absence of 1μg/mL of LPS. At the end of each time point, cell adhesion and growth were evaluated by means of optical microscope observations and MTT assay. The secretion levels of cytokines interleukin (IL)-1β and IL-6 and human β-defensins 1 and 2 were measured by specific enzyme-linked immunosorbent assay. Finally, an invitro scratch wound assay was performed to investigate the effect of α-tocopherol on fibroblast migration. α-tocopherol alone had no adverse effect on cell adhesion and morphology. Fibroblast proliferation increased in the presence of α-tocopherol with and without LPS. α-tocopherol alone had no effect on inflammatory cytokine (IL-1β and IL-6) secretion. Interestingly, following cell exposure to P.gingivalis LPS, α-tocopherol significantly (p<0.01) decreased the secretion of these two cytokines and increased human β-defensin-1 and -2 secretion. Finally, α-tocopherol increased the healing rate of the gingival fibroblasts from 12h up to 48h. These results suggest that α-tocopherol may play an active role in countering the damaging effect of LPS by reducing inflammatory cytokines, increasing β-defensins and promoting fibroblast growth, migration and wound healing.

SH2B1β Interacts with STAT3 and Enhances Fibroblast Growth Factor 1-Induced Gene Expression during Neuronal Differentiation

Neurite outgrowth is an essential process during neuronal differentiation as well as neuroregeneration. Thus, understanding the molecular and cellular control of neurite outgrowth will benefit patients with neurological diseases. We have previously shown that overexpression of the signaling adaptor protein SH2B1β promotes fibroblast growth factor 1 (FGF1)-induced neurite outgrowth (W. F. Lin, C. J. Chen, Y. J. Chang, S. L. Chen, I. M. Chiu, and L. Chen, Cell. Signal. 21:1060-1072, 2009). SH2B1β also undergoes nucleocytoplasmic shuttling and regulates a subset of neurotrophin-induced genes. Although these findings suggest that SH2B1β regulates gene expression, the nuclear role of SH2B1β was not known. In this study, we show that SH2B1β interacts with the transcription factor, signal transducer, and activator of transcription 3 (STAT3) in neuronal PC12 cells, cortical neurons, and COS7 fibroblasts. By affecting the subcellular distribution of STAT3, SH2B1β increased serine phosphorylation and the concomitant transcriptional activity of STAT3. As a result, overexpressing SH2B1β enhanced FGF1-induced expression of STAT3 target genes Egr1 and Cdh2. Chromatin immunoprecipitation assays further reveal that, in response to FGF1, overexpression of SH2B1β promotes the in vivo occupancy of STAT3-Sp1 heterodimers at the promoter of Egr1 and Cdh2. These findings establish a central role of SH2B1β in orchestrating signaling events to transcriptional activation through interacting and regulating STAT3-containing complexes during neuronal differentiation.

The influence of surface nanoroughness, texture and chemistry of TiZr implant abutment on oral biofilm accumulation.

The aim of the study was to examine surface nanoroughness, texture and chemistry of dental implant abutment and to investigate how these parameters influence oral biofilm formation in healthy subjects. Eight different nanorough TiZr surfaces were produced by polishing, machining, cathodic polarization and acid etching. Surface topography was examined using field emission scanning electron microscope and a blue light laser profilometer. Surface chemistry was analyzed by secondary ion mass spectrometry and X-ray photoelectron spectroscopy. Surface hydrophilicity was tested by measuring contact angle on the surfaces. A human in vivo study using a splint model was employed to evaluate oral biofilm accumulation on these surfaces. Different surface textures (flat, grooved and irregular) were created with nanoroughness from 29 to 214 nm. Some test surfaces were incorporated with hydrogen by cathodic polarization and/or acid etching with HCl/H(2)SO(4). Nanoroughness (S(a)) positively correlated with microbial adhesion. Biofilm accumulation was less pronounced on flat and grooved than on irregular surfaces. No significant association between hydrogen content or hydrophilicity of the surface and biofilm accumulation was observed. Nanoroughness (< 214 nm) and surface texture influence oral biofilm accumulation independent of surface chemistry and hydrophilicity. Surface hydrogen, which has previously been shown to promote fibroblast growth, does not affect biofilm formation.

Increased frequency of Th17 cells in systemic sclerosis is related to disease activity and collagen overproduction

IntroductionAlthough immune dysfunction plays a role in the pathogenesis of systemic sclerosis (SSc), involvement of T helper 17 (Th17) and T regulatory (Treg) cells remains unclear. We aimed to investigate the presence of Th17 and Treg cells in SSc patients and the role of Th17 cells in collagen production in SSc fibroblasts.MethodsWe analyzed inflammatory cell profiles in the skin of 13 SSc patients by immunohistochemistry, the percentage of Th17 and Treg cells in peripheral blood mononuclear cells (PBMCs) of 45 SSc patients and 24 healthy controls by flow cytometry, gene expression in PBMCs by real-time reverse transcription-polymerase chain reaction and interleukin-17 (IL-17) in sera and culture supernatants by enzyme-linked immunosorbent assay. We also investigated the effect of Th17 cell-derived IL-17 on fibroblast growth and collagen production.ResultsInfiltration of inflammatory cells including IL-17+ and Foxp3+ lymphocytes was detected in the skin of patients with early SSc. The percentages of circulating Th17 cells and IL-17 production were elevated in samples from patients with active SSc, whereas the percentage of circulating Treg cells was not affected. The number of Th17 cells was closely related to disease activity. IL-17 from SSc patients promoted fibroblast growth and collagen production, whereas IL-17 neutralizing antibody effectively blocked collagen production.ConclusionSSc progression might be linked to expansion of circulating Th17 cells and increased infiltration of IL-17+ cells in skin. Th17-derived IL-17 is involved in fibroblast growth and collagen production. IL-17 blocking antibody may be a useful tool for intervention in the fibrotic course of SSc.

Inorganic polyphosphate adsorbed onto hydroxyapatite for guided bone regeneration: An animal study

Inorganic polyphosphate (poly(P)) is recognized as a therapeutic agent that promotes fibroblast growth factor and enhances osteogenic differentiation, and in vivo, when adsorbed onto interconnected porous calcium hydroxyapatite (IP-CHA) enhances bone regeneration. The present study focused on the effect of poly(P) adsorbed onto IP-CHA granules (Poly(P)/IP-CHA) in guided bone regeneration (GBR). Dental implants were placed into the edentulous mandibular areas of five Beagle-Labrador hybrid dogs with screw expose on the buccal side, and then bone defects were filled Poly(P)/IP-CHA (test) or IP-CHA (control). After 12 weeks, histological evaluation and histomorphometrical analysis were performed. Newly-bone formation around exposed implant screw was clearly detected in the test-group. The ratio for regenerated bone height in the test group versus the control-group was 85.6±20.2 and 62.6±23.8, respectively, with no significant difference, while, that for bone implant contact was significantly higher (67.9±11.8 and 48.8±14.1, respectively). These findings indicate that Poly(P)/IP-CHA enhances bone regeneration in GBR.

Brittlestars contain highly sulfated chondroitin sulfates/dermatan sulfates that promote fibroblast growth factor 2-induced cell signaling

Glycosaminoglycans (GAGs) isolated from brittlestars, Echinodermata class Ophiuroidea, were characterized, as part of attempts to understand the evolutionary development of these polysaccharides. A population of chondroitin sulfate/dermatan sulfate (CS/DS) chains with a high overall degree of sulfation and hexuronate epimerization was the major GAG found, whereas heparan sulfate (HS) was below detection level. Enzymatic digestion with different chondroitin lyases revealed exceptionally high proportions of di- and trisulfated CS/DS disaccharides. The latter unit appears much more abundant in one of four individual species of brittlestars, Amphiura filiformis, than reported earlier in other marine invertebrates. The brittlestar CS/DS was further shown to bind to growth factors such as fibroblast growth factor 2 and to promote FGF-stimulated cell signaling in GAG-deficient cell lines in a manner similar to that of heparin. These findings point to a potential biological role for the highly sulfated invertebrate GAGs, similar to those ascribed to HS in vertebrates.