Comparison of Oncostatin M in Patients with Chronic Periodontitis with and without Diabetes

Abstract Objective: To compare the Oncostatin M (OSM) concentrations in tissues of patients with chronic periodontitis with and without diabetes. Material and Methods: Sixty-four subjects visiting the dental outpatient department were categorized as "healthy" (Group 1), "periodontitis" (Group 2), and "diabetes with periodontitis" (Group 3) groups. The clinical oral examination included assessment of plaque, gingivitis, probing depth, clinical attachment level. Blood glucose was assessed for group 3 patients. OSM concentration in the tissues was assessed using ELISA in all groups. Results: The mean OSM was 0.02 ± 0.04 pg/mg in the healthy group, 0.12 ± 0.09 pg/mg in the chronic periodontitis group and 0.13 ± 0.10 pg/mg in the diabetes-periodontitis group. A significantly higher mean OSM was seen in Group 2 and Group 3 than Group 1. The amount of OSM positively correlated with probing depth and clinical attachment level. Conclusion: Periodontal disease causes a rise in Oncostatin M, independent of the diabetic status. Expression of OSM in the gingival tissues can serve as an inflammatory marker.

Relationships among oncostatin M, insulin resistance, and chronic inflammation: a pilot study

ABSTRACT Objective Activated macrophages (M1-type macrophages) in adipose tissue secrete many proinflammatory cytokines that induce insulin resistance (IR). Oncostatin M (OSM), a member of the interleukin-6 (IL-6) family of Gp130 cytokines, plays an important role in a variety of biological functions, including the regulation of inflammatory responses. Proinflammatory cytokines released in patients with IR trigger a chronic, low-grade inflammatory reaction in blood vessel walls. This inflammator response leads to endothelial damage, which is the main mechanism for atherosclerosis and many cardiovascular diseases. Animal studies have reported a relationship between OSM and IR. To the best of our knowledge, however, few clinical studies have examined this topic. Therefore, we studied the relationship between serum levels of OSM and IR. Subjects and methods This prospective cross-sectional case-control study enrolled 50 people with IR (according to the HOMA-IR and QUICKI indices) and 34 healthy controls. The fasting blood concentrations of insulin, glucose, blood urea nitrogen (BUN), creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride, total cholesterol, C-reactive protein (CRP), and OSM were determined. Results There were no significant differences between the two groups in age, sex, and HbA1c levels. Univariate analyses showed that waist circumference (WC) and levels of fasting glucose, insulin, CRP, HDL-C, OSM, HOMA-IR, and QUICKI differed between the two study groups. In multivariate analyses, both IR indices (QUICKI and HOMA) and OSM differed between the two groups. Conclusion OSM was correlated with the IR indices (QUICKI and HOMA). For simplicity, it might replace the other IR indices in the future. Further detailed studies are needed to confirm this.

Elastase-Positive Neutrophils Are Associated With Refractoriness of Chronic Rhinosinusitis With Nasal Polyps in an Asian Population

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.

Effects of Oncostatin M on Invasion of Primary Trophoblasts under Normoxia and Hypoxia Conditions

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.

Differentiation Potential of Breast Milk-Derived Mesenchymal Stem Cells into Hepatocyte-Like Cells

Human breast milk stem cells (hBSCs) contain a population of cells with the ability to differentiate into various cell lineages for cell therapy applications. The current study examined the differentiation potential of hBSCs into hepatocytes- like cells. The cells were isolated from the breast milk and were treated with hepatogenic medium containing hepatocyte growth factor, insulin-like growth factor and dexamethasone for 7 days subsequently; Oncostatin M was added to the culture media. RT-PCR and immunocytochemistry were performed to detect the hepatogenic markers. The glycogen storage and the ability of the cells to absorb and release indocynanin green were also tested. The data showed that most of the differentiated cells formed cell aggregates after the 30th day, with more cells accumulated to form spheroids. RT-PCR revealed the expression of the hepatic nuclear factor, albumin, cytokeratin 18 and 19, cytochrome P2B6, glucose-6-phospahtase and claudin. The functional assays also showed glycogen storage and omission of indicynine green. Our study demonstrated hBSCs are novel population that can differentiate into hepatocyte-like cells.

STAT3 and ERK Signaling Pathways Are Implicated in the Invasion Activity by Oncostatin M through Induction of Matrix Metalloproteinases 2 and 9

PURPOSE: Our previous studies have shown that oncostatin M (OSM) promotes trophoblast invasion activity through increased enzyme activity of matrix metalloproteinase (MMP)-2 and -9. We further investigated OSM-induced intracellular signaling mechanisms associated with these events in the immortalized human trophoblast cell line HTR8/SVneo. MATERIALS AND METHODS: We investigated the effects of OSM on RNA and protein expression of MMP-2 and -9 in the first-trimester extravillous trophoblast cell line (HTR8/SVneo) via Western blot. The selective signal transducer and activator of transcription (STAT)3 inhibitor, stattic, STAT3 siRNA, and extracellular signal-regulated kinase (ERK) siRNA were used to investigate STAT3 and ERK activation by OSM. The effects of STAT3 and ERK inhibitors on OSM-induced enzymatic activities of MMP-2 and -9 and invasion activity were further determined via Western blot and gelatin zymography. RESULTS: OSM-induced MMP-2 and -9 protein expression was significantly suppressed by STAT3 inhibition with stattic and STAT3 siRNA silencing, whereas the ERK1/2 inhibitor (U0126) and ERK silencing significantly suppressed OSM-induced MMP-2 protein expression. OSM-induced MMP-2 and MMP-9 enzymatic activities were significantly decreased by stattic pretreatment. The increased invasion activity induced by OSM was significantly suppressed by STAT3 and ERK1/2 inhibition, though to a greater extent by STAT3 inhibition. CONCLUSION: Both STAT3 and ERK signaling pathways are involved in OSM-induced invasion activity of HTR8/SVneo cells. Activation of STAT3 appears to be critical for the OSM-mediated increase in invasiveness of HTR8/SVneo cells.

Influence of different body positions in vital capacity in patients on postoperative upper abdominal / Influência de diferentes posições corporais na capacidade vital em pacientes no pós-operatório abdominal superior / Influencia de diferentes posiciones corporales en la capacidad vital en pacientes en el postoperatorio abdominal superior

RATIONALE: The changes in body position can cause changes in lung function, and it is necessary to understand them, especially in the postoperative upper abdominal surgery, since these patients are susceptible to postoperative pulmonary complications. OBJECTIVE: To assess the vital capacity in the supine position (head at 0° and 45°), sitting and standing positions in patients in the postoperative upper abdominal surgery. METHODS: A cross-sectional study conducted between August 2008 and January 2009 in a hospital in Salvador/BA. The instrument used to measure vital capacity was analogic spirometer, the choice of the sequence of positions followed a random order obtained from the draw of the four positions. Secondary data were collected from the medical records of each patient. RESULTS: The sample consisted of 30 subjects with a mean age of 45.2 ± 11.2 years, BMI 20.2 ± 1.0 kg/m2. The position on orthostasis showed higher values of vital capacity regarding standing (mean change: 0.15 ± 0.03 L; p = 0.001), the supine to 45 (average difference: 0.32 ± 0.04 L; p = 0.001) and 0° (0.50 ± 0.05 L; p = 0.001). There was a positive trend between the values of forced vital capacity supine to upright posture (1.68 ± 0.47; 1.86 ± 0.48; 2.02 ± 0.48 and 2.18 ± 0.52 L; respectively). CONCLUSION: Body position affects the values of vital capacity in patients in the postoperative upper abdominal surgery, increasing in postures where the chest is vertical. .

JUSTIFICATIVA: As alterações no posicionamento corporal podem ocasionar mudanças na função respiratória e é necessário compreendê-las, principalmente no pós-operatório abdominal superior, já que os pacientes estão suscetíveis a complicações pulmonares pós-operatórias. OBJETIVO: Verificar a capacidade vital nas posições de decúbito dorsal (cabeceira a 0° e 45°), sentado e em ortostase em pacientes no pós-operatório de cirurgia abdominal superior. MÉTODOS: Estudo transversal, feito entre agosto de 2008 e janeiro de 2009, em um hospital na cidade de Salvador (BA). O instrumento usado para mensuração da capacidade vital (CV) foi o ventilômetro analógico e a escolha da sequência das posições seguiu uma ordem aleatória obtida a partir de sorteio das quatro posições. Os dados secundários foram colhidos nos prontuários de cada paciente. RESULTADOS: A amostra foi composta por 30 indivíduos com idade média de 45,2 ± 11,2 anos e IMC 20,2 ± 1,0 kg/m2. A posição em ortostase apresentou valores maiores da CV em relação à sedestração (média das diferenças: 0,15 ± 0,03 litros; p = 0,001), ao decúbito dorsal a 45° (média das diferenças: 0,32 ± 0,04 litros; p = 0,001) e 0° (0,50 ± 0,05 litros; p = 0,001). Houve um aumento positivo entre os valores de CVF do decúbito dorsal para a postura ortostática (1,68 ± 0,47; 1,86 ± 0,48; 2,02 ± 0,48 e 2,18 ± 0,52 litros; respectivamente). CONCLUSÃO: A posição do corpo afeta os valores da CV em pacientes no pós-operatório de cirurgia abdominal superior, com aumento nas posturas em que o tórax encontra-se verticalizado. .

JUSTIFICACIÓN: Las alteraciones en el posicionamiento corporal pueden ocasionar cambios en la función respiratoria y es necesario comprenderlas, principalmente en el postoperatorio abdominal superior, ya que los pacientes son susceptibles a complicaciones pulmonares postoperatorias. OBJETIVO: Verificar la capacidad vital en las posiciones de decúbito dorsal (cabeza a 0° y 45°), sentado y en ortostasis en pacientes en el postoperatorio de cirugía abdominal superior. MÉTODOS: Estudio transversal realizado entre agosto de 2008 y enero de 2009, en un hospital en la ciudad de Salvador (BA). El instrumento usado para la medición de la capacidad vital (CV) fue el espirómetro analógico y la elección de la secuencia de las posiciones siguió un orden aleatorio que se obtuvo a partir de un sorteo de las 4 posiciones. Los datos secundarios fueron extraídos de las historias clínicas de cada paciente. RESULTADOS: La muestra se compuso de 30 individuos con edades medias de 45,2 ± 11,2 años e IMC de 20,2 ± 1 kg/m2. La posición en ortostasis presentó valores mayores de CV con relación a la posición sedente (media de las diferencias: 0,15 ± 0,03 L; p = 0,001), al decúbito dorsal a 45° (media de las diferencias: 0,32 ± 0,04 L; p = 0,001) y a 0° (0,50 ± 0,05 L; p = 0,001). Hubo un aumento positivo entre los valores de CV forzada del decúbito dorsal para la postura ortostática (1,68 ± 0,47; 1,86 ± 0,48; 2,02 ± 0,48 y 2,18 ± 0,52 L, respectivamente). CONCLUSIÓN: La posición del cuerpo afecta los valores de la CV en pacientes durante el postoperatorio de cirugía abdominal superior, con aumento en las posturas en las que el tórax está verticalizado. .

SKI306X inhibition of glycosaminoglycan degradation in human cartilage involves down-regulation of cytokine-induced catabolic genes

BACKGROUND/AIMS: SKI306X, a mixed extract of three herbs, Clematis mandshurica (CM), Prunella vulgaris (PV), and Trichosanthes kirilowii (TK), is chondroprotective in animal models of osteoarthritis (OA). The objectives of this study were to investigate its effect on interleukin (IL)-1beta-induced degradation of glycosaminoglycan (GAG) and the basis of its action in human OA cartilage, as well as to screen for the presence of inhibitors of matrix metalloproteinase (MMP)-13 and a disintegrin and metalloprotease with thrombospondin motifs (ADAMTS)-4 in SKI306X and its component herbs, as well as in fractions from SKI306X. METHODS: Human OA chondrocytes and cartilage explants were obtained during total knee replacements and incubated with IL-1beta +/- oncostatin M with or without SKI306X or its component herb extracts. GAG degradation was assayed in cartilage explants using a commercial kit. Expression of genes involved in cartilage destruction was measured by real-time polymerase chain reaction using chondrocyte RNA. SKI306X was fractionated by preparative liquid chromatography to test for the presence of inhibitors of MMP-13 and ADAMTS-4. RESULTS: SKI306X and PV inhibited IL-1beta-induced GAG release from cartilage explants, and SKI306X, CM, PV, and TK inhibited IL-1beta-induced MMP gene expression. Unexpectedly, SKI306X greatly stimulated IL-1beta + oncostatin M-induced ADAMTS-4 gene expression, probably due to its TK component. Some fractions of SKI306X also inhibited ADAMTS-4 activity. CONCLUSIONS: SKI306X and its herbal components inhibit GAG degradation and catabolic gene expression in human OA chondrocytes and cartilage explants. SKI306X likely also contains one or more ADAMTS-4 inhibitor.

Expression of cytokines of interleukin-6 family in gingival fibroblasts by Toll-like receptor-2 / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To investigate whether signaling through Toll-like receptor-2 (TLR-2) can affect the expression of some cytokines in human gingival fibroblasts.</p><p><b>METHODS</b>The gingival fibroblasts were isolated and cultured in vivo, divided into blank control group, lipopolysaccharide (LPS) from Porphyromonas gingivalis (Pg) group and Escherichia coli (Ec) group. mRNA expression levels were measured by real-time polymerase chain reaction (PCR). The protein expression levels were detected by the enzyme linked immunosorbent assay (ELISA). The data was statistically analyzed by SPSS16.0 software package.</p><p><b>RESULTS</b>LPS from Pg could stimulate the expression of interleukin (IL)-6 and leukemia inhibitory factor (LIF) mRNA and protein, which reached the peak (5.87 ± 0.83) at 10 h, and the expression level increased with the increase of the Pg concentration. IL-11 or oncostatin-M (OSM) mRNA expression was not affected by LPS. After treated with Pg for 48 h, the protein expression of IL-6 and LIF was up-regulated, (962 ± 57) ng/L and (47 ± 18) ng/L respectively.</p><p><b>CONCLUSIONS</b>Signaling through TLR-2 controls the expression of cytokines of IL-6 family in human gingival fibroblasts.</p>

Association of the Oncostatin M Receptor Gene Polymorphisms with Papillary Thyroid Cancer in the Korean Population

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.

Correlation of levels of oncostatin M cytokine in crevicular fluid and serum in periodontal disease / 国际口腔科学杂志·英文版

<p><b>AIM</b>The 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).</p><p><b>METHODOLOGY</b>60 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).</p><p><b>RESULTS</b>It 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.</p><p><b>CONCLUSION</b>Increased 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.</p>

[Induction of differentiation of bone marrow mesenchymal stem cells of rat into hepatocyte and study of their biochemical factors]

Bone marrow mesenchymal stem cells [MSCs] are multi potential and capable of differentiating into specialized tissues. The aim of this study was to investigate the induction of differentiation of the bone marrow MSCs of rat into hepatocytes by use of fibroblast growth factor-2 [bFGF], hepatocyte growth factor [HGF] and oncostatin M [OSM] in order to find a suitable source of hepatoecytes for bioartificial liver or liver transplantation. In this research MSCs were obtained from the bone marrow of rat and cultured in DMEM-LG medium supplemented with 15% FBS. These cells were treated with differential medium supplemented with HGF, bFGF and OSM for 24 days. Morphology, RT-PCR and Biochemical assays were used to identify the differentiation of stem cells into hepatic cells. Result: MSCs took a round shape after differentiation, while undifferentiated cells had fibroblast-like morphology. Albumin, urea and alpha-fetoprotein [AFP] were detected in differentiated cells. Alkaline phosphatase activity was confirmed by biochemical tests. The mRNA expression of CK-18 and tyrosine amino transferase [TAT] in differentiated cells was demonstrated by RT-PCR after induction. The rat MSCs from bone marrow can differentiate into hepatocyte-like cells in the presence of HGF, bFGF and OSM in vitro. Cytokines may play an important role in differentiation of bone marrow MSCs of rat into hepatocytes. Bone marrow derived MSCs are a new source of cell types which can be used for cell transplantation in hepatic diseases

Effect of Oncostatin M on Proliferation and Matrix Synthesis of Dermal Fibroblasts

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.

Effect of Oncostatin M on Wound Healing Activity of Diabetic Fibroblasts in vitro

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.

Hematopoietic growth factors expressed in human aorta-gonad-mesonephros (AGM)-derived stromal cells in vitro / 中国实验血液学杂志

This study was aimed to investigate the hematopoietic growth factors expressed in human aorta-gonad-mesonephros (AGM)-derived stromal cells in vitro in order to provide the basic data for elucidating the role of AGM -derived-stromal cells in embryo-hematopoiesis and its hematopoietic suppoitive effect. RT-PCR was used to analyze the expression of IL-6, SCF, Flt3-L, oncostatin M (OSM), IL-3, TPO, M-CSF and LIF in human aorta-gonad-mesonephros-derived stromal cells (hAGMS1-S5) at mRNA level. IL-6, SCF and Flt3-L levels were detected in the supernatant of hAGMS1-S5 stromal cells by ELISA assay. Umbilical cord blood CD34(+) cells were cocultured with hAGMS1-S5 feeder cells, and hematopoietic cells were collected at day 14 for colony analysis in methylcellulose semisolid medium. The results showed that human aorta-gonad-mesonephros-derived stromal cells S1-S5 expressed IL-6, SCF, Flt3-L and OSM mRNA, but did not express IL-3, TPO, M-CSF and LIF mRNA. In the supernatant of hAGMS1-S5 cells, IL-6, SCF and Flt3-L could be detected by ELISA assay at different levels, while there was no significant difference between groups of hAGMS1-S5 (P > 0.05). When cocultured with umbilical cord blood CD34(+) cells, hAGMS1-S5 could support the expansion of CFU-GM, BFU-E, and CFU-Mix. The supportive effects of hAGM S1-S5 were significantly different (P < 0.05), hAGM S3 and S4 were better than hAGM S1, S2, and S5. It is concluded that detection of hematopoietic growth factors expressed in human aorta-gonad-mesonephros-derived stromal cells provided a solid foundation to elucidate the mechanism of hematopoiesis and the hematopoietic supportive effect of these stromal cells.

E14 mouse embryonic stem cells differentiate into hepatocyt ESC / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate in vitro methods of inducing mouse embryonic stem cell(s) (ESC) into hepatocytes.</p><p><b>METHODS</b>E14 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.</p><p><b>RESULTS</b>Morphology 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.</p><p><b>CONCLUSION</b>ESC-derived hepatic cells possess characteristics of hepatocytes, which would promise the eventual clinical use of ESC in treating damaged liver tissues.</p>

Control of angiogenesis by inhibitor of phospholipase A2 / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the potential effects of angiogenic process by secretory phospholipase A2 (sPLA2) inhibitor-HyPE (linking N-derivatized phosphatidyl-ethanolamine to hyaluronic acid) on human bone marrow endothelial cell line (HBME-1).</p><p><b>METHODS</b>In order to examine the suppressing effects of HyPE on HBME-1 proliferation, migration, and capillary-like tube formation, HBME-1 were activated hy angiogenic factor, specifically by basic fibroblast growth factor (b-FGF), vascular endothelial growth factor (VEGF), and oncostatin M (OSM) (at a final concentration of 25, 20, and 2.5 ng/mL, respectively), then HBME-1 proliferation, migration, and tube formation were studied in the absence or presence of HyPE. HBME-1 tube formation was specially analyzed in fibrin gel.</p><p><b>RESULTS</b>HyPE effectively inhibited HBME-1 proliferation and migration as a dose-dependent manner, whatever HBME-1 were grown in the control culture medium or stimulated with b-FGF, VEGF, or OSM. In fibrin, the formations of HBME-1 derived tube-like structures were enhanced by all angiogenic factors, but these were strongly suppressed by HyPE.</p><p><b>CONCLUSIONS</b>The results support the involvement of sPLA2 in angiogenesis. It is proposed that sPLA2 inhibitor introduces a novel approach in the control of cancer development.</p>

Profiling of Differentially Expressed Genes in Human Polymorphonuclear Leukocyte on Human Amniotic Membrane

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.