OBJECTIVES: To investigate the association between papillary thyroid cancer (PTC) and single nucleotide polymorphisms (SNPs) of oncostatin M receptor (OSMR) in the Korean population. METHODS: Retrospective case-control study was done. Eighty-five patients with PTC and 287 controls were studied. One missense SNP (rs2278329, Asp553Asn) and one promoter SNP (rs2292016, -100 G/T) of the OSMR gene were genotyped by direct sequencing. Genetic data were analyzed using the SNPStats, Helixtree, and SNPAnalyzer Pro. PTC patients were dichotomized and compared with respect to the clinicopathologic characteristics. RESULTS: There was no association between genotypes and allele frequencies of OSMR SNPs (rs2278329 and rs2292016) and PTC susceptibility. SNP rs2278329 was significantly associated with tumor size (dominant model; P=0.028; odds ratio [OR], 2.71; 95% confidence interval [CI], 1.12 to 6.57). The A allele was higher in sizes large than 1 cm (32.5% vs. 16.7%; P=0.018; OR, 2.41; 95% CI, 1.17 to 4.98). Regarding the number of tumors, we found no significant association with genotype, however, the A allele was higher in patients with multifocaltiy (33.3% vs. 19.1%; P=0.040; OR, 2.12; 95% CI, 1.03 to 4.34). CONCLUSION: The results suggest that OSMR polymorphism rs2278329 is associated with clinicopathologic characteristics of the tumor growth and multifocality development.
Alleles ; Case-Control Studies ; Factor IX ; Gene Frequency ; Genotype ; Humans ; Odds Ratio ; Oncostatin M ; Polymorphism, Single Nucleotide ; Receptors, Oncostatin M ; Retrospective Studies ; Thyroid Gland ; Thyroid Neoplasms

PURPOSE: Oncostatin M(OSM) is a multifunctional cytokine that belongs to the interleukin(IL)-6 family. Although there have been a number of studies that focused on the role and mechanism of OSM in various organs and tissues, there are few reports on its effect on wound healing. The final purpose of this project is to evaluate the effect of OSM on wound healing. This pilot study was designed to investigate the effect of OSM on proliferation and matrix synthesis of human dermal fibroblasts, which are the major components of the wound healing. METHODS: Excess skin that was obtained from patients who underwent skin grafts, was used for this study. From this material, fibroblasts were isolated and cultured. The cultured fibroblasts were treated with one of four concentrations of OSM. The OSM concentrations used were 0, 50, 100, and 200ng/ml, respectively. After the OSM treatment, cell proliferation was determined by the MTT assay, collagen synthesis by the C1CP method, GAG levels by the Blyscan Dye method. The parameter levels of each group were compared. RESULTS: OSM treatment increased all the components tested in the study. In particular, cell proliferation, GAG synthesis demonstrated statistically significant increases(p<0.05 in the Mann-Whitney U-test). The highest increase in all the components was obtained at a 100ng/ml concentration of OSM. CONCLUSION: The results of the present study indicate that OSM stimulates proliferation and matrix synthesis of human dermal fibroblast and the optimal concentration for wound healing is 100ng/mL.
Cell Proliferation ; Collagen ; Fibroblasts ; Humans ; Oncostatin M ; Pilot Projects ; Skin ; Transplants ; Wound Healing

PURPOSE: To investigate the effect of oncostatin M (OSM) on protein expression levels and enzymatic activities of matrix metalloprotainase (MMP)-2 and MMP-9 in primary trophoblasts and the invasiveness thereof under normoxia and hypoxia conditions. MATERIALS AND METHODS: Protein expression levels and enzymatic activities of MMP-2 and MMP-9 in primary trophoblasts under normoxia and hypoxia conditions were examined by Western blot and zymography, respectively. Effects of exogenous OSM on the in vitro invasion activity of trophoblasts according to oxygen concentration were also determined. Signal transducer and activator of transcription 3 (STAT3) siRNA was used to determine whether STAT3 activation in primary trophoblasts was involved in the effect of OSM. RESULTS: OSM enhanced protein expression levels and enzymatic activities of MMP-2 and MMP-9 in term trophoblasts under hypoxia condition, compared to normoxia control (p < 0.05). OSM-induced MMP-2 and MMP-9 enzymatic activities were significantly suppressed by STAT3 siRNA silencing under normoxia and hypoxia conditions (p < 0.05). Hypoxia alone or OSM alone did not significantly increase the invasiveness of term trophoblasts. However, the invasion activity of term trophoblasts was significantly increased by OSM under hypoxia, compared to that without OSM treatment under normoxia. CONCLUSION: OSM might be involved in the invasiveness of extravillous trophoblasts under hypoxia conditions via increasing MMP-2 and MMP-9 enzymatic activities through STAT3 signaling. Increased MMP-9 activity by OSM seems to be more important in primary trophoblasts.
Anoxia* ; Blotting, Western ; In Vitro Techniques ; Oncostatin M* ; Oxygen ; RNA, Small Interfering ; STAT3 Transcription Factor ; Trophoblasts*

PURPOSE: Oncostatin M(OSM) has been known as a role in fibrosis and anti-inflammatory effects of various organs and tissues. Although there have been a number of studies which are focused on the roles and mechanisms of OSM, there are few reports on its effects in chronic wound healing. The purpose of this study is to evaluate the effects of OSM in wound healing activities of dermal fibroblasts of chronic wound in vitro. In particular, this study is focused on cell proliferation and synthesis of collagen and glycosaminoglycan(GAG), which are the major components of the extracellular matrices, of diabetic fibroblasts. METHODS: Fibroblasts were isolated from excess skin that was obtained from diabetic foot ulcer patients who underwent debridement. The isolated fibroblasts were cultivated in presence of OSM(100ng/mL). Cell proliferation, collagen synthesis and GAG levels were compared. RESULTS: All the components tested in this study increased in OSM treatment group. In particular, collagen and GAG synthesis demonstrated statistically significant increases(p<0.05 in the Mann-Whitney U- test). CONCLUSION: These results indicate that OSM increases wound healing activities of dermal fibroblasts of chronic wound in vitro.
Cell Proliferation ; Collagen ; Debridement ; Diabetic Foot ; Extracellular Matrix ; Fibroblasts ; Fibrosis ; Humans ; Oncostatin M ; Skin ; Ulcer ; Wound Healing

BACKGROUND: Although several studies have shown the role of interleukin-31 (IL-31) and its receptors in inducing pruritus in certain skin disorders, knowledge of its role in post-burn hypertrophic scars is insufficient. Therefore, the histopathological expression levels of IL-31, IL-31 receptor alpha (IL-31RA), and oncostatin M receptor (OSMR) in post-burn hypertrophic scar tissues were investigated and compared with normal tissue expression levels. METHODS: Samples of hypertrophic scar tissue were obtained from 20 burn patients through punch biopsy. Normal samples were obtained from areas adjacent to the burn injury site of the same patients. Samples were placed in 10% neutral buffered formalin, embedded in paraplast, and processed into serial 5-μm sections. Immunohistochemistry results were semi-quantitatively evaluated for IL-31, IL-31RA, and OSMR. By hematoxylin and eosin staining, epidermal and dermal thickness were assessed with a microscope and digital camera. Intensities were rated on a scale of 1 to 4. RESULTS: Percentages for IL-31, IL-31RA, and OSMR in the epidermal basal layer cell cytoplasm were significantly greater in the burn scar tissue compared to normal skin, as well as the dermal and epidermal thickness (p < .05). There was a significant difference in IL-31 epidermal basal layer intensity in burn scar tissue compared to normal skin (p < .05). Besides the OSMR basal layer intensity, IL-31 and IL-31RA intensities between the burn scar and normal tissues were not significant. However, correlations were significant, indicating that the greater the infiltration percentage, the higher the intensity (p < .05). CONCLUSIONS: IL-31, IL-31RA, and OSMR expression levels are increased in hypertrophic scars compared with normal tissue.
Biopsy ; Burns ; Cicatrix ; Cicatrix, Hypertrophic ; Cytoplasm ; Eosine Yellowish-(YS) ; Formaldehyde ; Hematoxylin ; Humans ; Immunohistochemistry ; Pruritus ; Receptors, Oncostatin M ; Skin

OBJECTIVETo investigate in vitro methods of inducing mouse embryonic stem cell(s) (ESC) into hepatocytes.

METHODSE14 mouse ESC were cultivated in suspension and plated to form aggregates, the embryoid bodies. They were allowed to outgrow on the plated culture with the stepwise addition of growth factors-- acidic fibroblast growth factor (aFGF), hepatocyte growth factor (HGF) and oncostatin M (OSM) into the culture medium. Morphology was investigated by phase contrast microscopy. Gene expressions of endodermal and liver specific mRNA were analyzed by reverse transcription-polymerase chain reaction (RT-PCR). Indocyanine green (ICG) uptake assay and periodic acid-Schiff reaction (PAS) were performed to assess the differentiation and function of the cells.

RESULTSMorphology analysis revealed a difference between ESC-derived hepatic cells and original ESC in that the former showed distinct round or polygonal shapes with clear boundaries, some arranged tightly in cords, while the latter grew in clones without clear boundaries between cells. Those ESC-derived hepatic cells expressed endodermal and liver specific genes mRNA--TTR, AAT, AFP, ALB, G6P and TAT. ICG uptake assay and PAS reaction were positive for those ESC-derived hepatic cells. The ICG positive cells were about 85.1% in number.

CONCLUSIONESC-derived hepatic cells possess characteristics of hepatocytes, which would promise the eventual clinical use of ESC in treating damaged liver tissues.

Animals ; Cell Differentiation ; physiology ; Cells, Cultured ; Cytokines ; pharmacology ; Embryo, Mammalian ; Fibroblast Growth Factor 1 ; pharmacology ; Hepatocyte Growth Factor ; pharmacology ; Hepatocytes ; cytology ; Mice ; Oncostatin M ; Stem Cells ; cytology

OBJECTIVETo assess the association of polymorphisms of oncostatin M receptor (OSMR) gene with dilated cardiomyopathy (DCM) in a Han Chinese population.

METHODSFor 351 DCM patients and 418 healthy controls, two single nucleotide polymorphisms (SNPs) of the OSMR gene, namely rs2292016 (promoter, -100G/T) and rs2278329 (missense, Asp553Asn), were genotyped with a TaqMan SNP genotyping assay. Two hundred of the patients were also followed up for (49.85 ± 22.52) months.

RESULTSFor rs2292016, carriers of GT genotype were more likely to develop DCM compared to those with GG and TT genotypes (OR=1.45, 95%CI: 1.09-1.92, P=0.01). For those who did not receive cardiac resynchronization therapy, the GG genotype of rs2292016 was an independent indicator for poor prognosis (OR=1.69, 95%CI: 1.11-2.63, P=0.017). No association was found between genotypes of rs2278329 with the susceptibility or prognosis of DCM.

CONCLUSIONPolymorphisms of the OSMR rs2292016 locus are related to the development and outcome of DCM.

Asian Continental Ancestry Group ; genetics ; Cardiomyopathy, Dilated ; etiology ; genetics ; China ; ethnology ; Genotype ; Humans ; Oncostatin M Receptor beta Subunit ; genetics ; Polymorphism, Single Nucleotide

AIMThe aim of this study was to measure the level of Oncostatin M (OSM) a gp130 cytokine in the gingival crevicular fluid (GCF) and serum of chronic periodontitis patients and to find any correlation between them before and after periodontal therapy (scaling and root planing, SRP).

METHODOLOGY60 subjects (age 25-50 years) were enrolled into three groups (n=20 per group), group I (healthy), group II (gingivitis) and group III (chronic periodontitis). Group III subjects were followed for 6-8 weeks after the initial periodontal therapy (SRP) as the group IV (after periodontal therapy). Clinical parameters were assessed as gingival index (GI), probing depth (PD), clinical attachment level (CAL), and radiographic evidence of bone loss. GCF and serum levels of OSM were measured by using Enzyme Linked Immunosorbent Assay (ELISA).

RESULTSIt was found that mean OSM levels had been elevated in both the GCF and serum of chronic periodontitis subjects (726.65 +/- 283.56 and 65.59 +/- 12.37 pg mL(-1), respectively) and these levels were decreased proportionally after the periodontal therapy (95.50 +/- 38.85 and 39.98 +/- 16.69 pg mL(-1) respectively). However, OSM was detected in GCF of healthy subjects (66.15 +/- 28.10 pg mL(-1)) and gingivitis-suffering subjects (128.33 +/- 22.96 pg mL(-1)) and was found as below the detectable limit (approximately equal 0.0 pg mL(-1)) in the serum of same subjects. Significant correlation has been found between clinical parameters and GCF-serum levels of OSM.

CONCLUSIONIncreased OSM level both in the GCF and serum, and the decreased levels after initial periodontal therapy (SRP) may suggest a use as an inflammatory biomarker in the periodontal disease.

Adult ; Analysis of Variance ; Case-Control Studies ; Chronic Periodontitis ; blood ; metabolism ; therapy ; Dental Scaling ; Female ; Gingival Crevicular Fluid ; chemistry ; Gingivitis ; blood ; metabolism ; therapy ; Humans ; Male ; Middle Aged ; Oncostatin M ; analysis ; blood ; metabolism ; Periodontal Index ; Statistics, Nonparametric

PURPOSE: To identify genes that showed altered expression between human polymorphonuclear (PMN) cell cultured on plastic and on amniotic membrane by the technique of differential hybridization of two Altas(TM) Human cDNA expression array. METHODS: 32P-labeled complimentary DNA probes derived from RNA of either human polymorphonuclear leukocyte cultured on plastic and cultured on amniotic membrane were hybridized to two identical human cDNA expression array membranes containing 588 known genes. RESULTS: Of the total 588 genes, 130 genes were up- or down-regulated. 50 up-regulated and 80 down-regulated genes were identified in polymorphonuclear leukocyte cultured on amniotic membrane compared with control. After different signal intensity was normalized more than 4000 by Atlas Image(TM) 1.0 Software, 19 genes were up-regulated and 36 genes down-regulated. CONCLUSIONS: Genes associated with the process of apoptosis, DNA synthesis and repair were down-regulated in PMN cultured on AM and genes associated with DNA binding protein, transcription factor were altered. Cell-cell communication factors including TGF-beta, PDGF-A, RANTES, MRP-14, oncostatin M, MIP-2 alpha were significantly down-regulated and cell surface antigen CD11a (LFA-1) was down-regulated, suggesting that AM can suppress the inflammatory reaction mediated by adhesion molecule, inflammatory, proinflammatory cytokines and chemokines.
Amnion* ; Antigens, Surface ; Apoptosis ; Chemokine CCL5 ; Chemokines ; Cytokines ; DNA ; DNA Probes ; DNA, Complementary ; DNA-Binding Proteins ; Humans* ; Inflammation ; Membranes ; Neutrophils* ; Oligonucleotide Array Sequence Analysis ; Oncostatin M ; Plastics ; RNA ; Transcription Factors ; Transforming Growth Factor beta

PURPOSE: Various immune cells, including eosinophils and neutrophils, are known to contribute to the development of chronic rhinosinusitis with nasal polyps (CRSwNP). However, the current understanding of the role of neutrophils in the development of CRSwNP still remains unclear. Therefore, we investigated risk factors for refractoriness of CRSwNP in an Asian population. METHODS: Protein levels of 17 neutrophil-related mediators in nasal polyps (NPs) were determined by multiplex immunoassay, and exploratory factor analysis using principal component analysis was performed. Immunofluorescence analysis was conducted to detect human neutrophil elastase (HNE) or myeloperoxidase (MPO)-positive cells. Tissue eosinophilic nasal polyp (ENP) and tissue neutrophilia (Neu(high)) were defined as greater than 70 eosinophils and 20 HNE-positive cells, otherwise was classified into non-eosinophilic nasal polyp (NENP) and absence of tissue neutrophilia (Neu(low)). RESULTS: In terms of disease control status, NENP-Neu(low) patients showed the higher rate of disease control than NENP-Neu(high) and ENP-Neu(high) patients. Linear by linear association demonstrated the trend in refractoriness from NENP-Neu(low) to NENP-Neu(high) or ENP-Neu(low) to ENP-Neu(high). When multiple logistic regression was performed, tissue neutrophilia (hazard ratio, 4.38; 95% confidence interval, 1.76-10.85) was found as the strongest risk factor for CRSwNP refractoriness. Additionally, exploratory factor analysis revealed that interleukin (IL)-18, interferon-γ, IL-1Ra, tumor necrosis factor-α, oncostatin M, and MPO were associated with good disease control status, whereas IL-36α and IL-1α were associated with refractory disease control status. In subgroup analysis, HNE-positive cells and IL-36α were significantly upregulated in the refractory group (P = 0.0132 and P = 0.0395, respectively), whereas MPO and IL-18 showed higher expression in the controlled group (P = 0.0002 and P = 0.0009, respectively). Moreover, immunofluorescence analysis revealed that IL-36R⁺HNE⁺-double positive cells were significantly increased in the refractory group compared to the control group. We also found that the ratio of HNE-positive cells to α1 anti-trypsin was increased in the refractory group. CONCLUSIONS: Tissue neutrophilia had an influence on treatment outcomes in the Asian CRSwNP patients. HNE-positive cells and IL-36α may be biomarkers for predicting refractoriness in Asians with CRSwNP. Additionally, imbalances in HNE and α1 anti-trypsin may be associated with pathophysiology of neutrophilic chronic rhinosinusitis.
Asian Continental Ancestry Group ; Biomarkers ; Eosinophils ; Fluorescent Antibody Technique ; Humans ; Immunoassay ; Interleukin 1 Receptor Antagonist Protein ; Interleukin-18 ; Interleukins ; Leukocyte Elastase ; Logistic Models ; Nasal Polyps ; Necrosis ; Neutrophils ; Oncostatin M ; Peroxidase ; Principal Component Analysis ; Rhinitis ; Risk Factors ; Sinusitis