BACKGROUND Oncostatin M(OSM)is a pleiotropic cytokine which is implicated in the path-ogenesis of inflammatory bowel disease(IBD).AIM To evaluate the prognostic role of OSM in IBD patients.METHODS Literature search wa...BACKGROUND Oncostatin M(OSM)is a pleiotropic cytokine which is implicated in the path-ogenesis of inflammatory bowel disease(IBD).AIM To evaluate the prognostic role of OSM in IBD patients.METHODS Literature search was conducted in electronic databases(Google Scholar,Embase,PubMed,Science Direct,Springer,and Wiley).Studies were selected if they reported prognostic information about OSM in IBD patients.Outcome data were synthesized,and meta-analyses were performed to estimate standardized mean differences(SMDs)in OSM levels between treatment responders and non-res-ponders and to seek overall correlations of OSM with other inflammatory bio-markers.RESULTS Sixteen studies(818 Crohn’s disease and 686 ulcerative colitis patients treated with anti-tumor necrosis factor-based therapies)were included.OSM levels were associated with IBD severity.A meta-analysis found significantly higher OSM levels in non-responders than in responders to therapy[SMD 0.80(0.33,1.27);P=0.001],in non-remitters than in remitters[SMD 0.75(95%CI:0.35 to 1.16);P<0.0001]and in patients with no mucosal healing than in those with mucosal heal-ing[SMD 0.63(0.30,0.95);P<0.0001].Area under receiver operator curve values showed considerable variability between studies but in general higher OSM levels were associated with poor prognosis.OSM had significant correlations with Simple Endoscopic Score of Crohn’s disease[r=0.47(95%CI:0.25 to 0.64);P<0.0001],Mayo Endoscopic Score[r=0.35(95%CI:0.28 to 0.41);P<0.0001],fecal calprotectin[r=0.19(95%CI:0.08 to 0.3);P=0.001],C-reactive protein[r=0.25(95%CI:0.11 to 0.39);P<0.0001],and platelet count[r=0.28(95%CI:0.17 to 0.39);P<0.0001].CONCLUSION OSM is a potential candidate for determining the severity of disease and predicting the outcomes of anti-tumor necrosis factor-based therapies in IBD patients.展开更多
In the present study, FBL3 murine erythroleukemia cells were transfected with human OSM(hOSM) gene by recombinant adenovirus, then the immunological properties of hOSM genetransfected FBL3 cells(FBL3OSM+) were investi...In the present study, FBL3 murine erythroleukemia cells were transfected with human OSM(hOSM) gene by recombinant adenovirus, then the immunological properties of hOSM genetransfected FBL3 cells(FBL3OSM+) were investigated. 4 hours after transfection with hOSM gene, hOSM could be detected in the supernatant of FBL3OSM+ cells and hOSM secretion peaked at 24 h. The proliferation of FBL3OSM+ cells was inhibited markedly. The clonal formation of FBL3OSM+ cells was suppressed more obviously in comparison with wildtype FBL3 cells when analysed in clonal argar culture. Flow cytometry analysis showed that FBL3OSM+ cells expressed higher levels of Fas protein, B7 and ICAM1 molecules.FBL3OSM+ cells also expressed higher level of MHC class I molecules(H2Kb) but remained unchanged in expression of MHC class II molecules (Ia). CD14, which is a specific marker of monocyte/macrophage and not expressed on the wildtype FBL3 cells, was also detected on the surface of FBL3OSM+ cells. The results suggested that OSM gene transfer could increase the immunogenicity of FBL3 cells and promote their differentiation into macrophagelike cells. The data outline a promising approach to OSM gene therapy of leukemia mediated by recombinant adenovirus.展开更多
Aim 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...Aim 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）. Methodology 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）. Results 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,res-pectively） 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 （≈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. Conclusion 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 bio-marker in the periodontal disease.展开更多
Purpose:Oncostatin M(OSM) is a cytokine released by macrophages and lymphocytesthat can function as a growth regulator. A current study shows that leukemia inhibitoryfactor (LIF), a homologue of OSM, can prevent photo...Purpose:Oncostatin M(OSM) is a cytokine released by macrophages and lymphocytesthat can function as a growth regulator. A current study shows that leukemia inhibitoryfactor (LIF), a homologue of OSM, can prevent photoreceptor cell death when expressedin the lens of transgenic mice. We determined the efforts of lens-specific overexpressionof OSM on the development of eye.Methods: A truncated mouse OSM cDNA ( ～ 660 bp) was linked to the αA-crytallinpromoter, and injected into single-cell embryos with microinjection. Then, transgenic micewere established. The mRNA expression of transgene OSM was detected by in situhybridization. Immunohistochemistry was used to detect the expression of syntaxin, glialfibrillary acidic protein (GFAP), synaptophysin in the retinas of transgenic mice.Results: At embryonic day (E 17.5), the expression of the syntaxin at the inner and midportion of the retinas of transgenic mice was much higher than that of the retinas ofnon-transgenic mice. The expression of GFAP was detected in the retinas of transgenicmice, while no expression in non-transgenic normal FVB(FVB/N) mice was detected inthis stage. At postnatal day one (P1), the expression of synaptophysin was detected inthe retinas of transgenic mice, but there was no such expression in FVB/N mice.Conclusions: Lens-specific overexpression of OSM induces premature differentiation ofamacrine cells, gial cells, and photoreceptors in vivo.展开更多
Background/Aims: Liver resection represents the treatment of choice for hepatocellular carcinoma (HCC) arising in well-compensated cirrhosis. Gene expression of the multifunctional cytokine, Oncostatin M (OSM), stimul...Background/Aims: Liver resection represents the treatment of choice for hepatocellular carcinoma (HCC) arising in well-compensated cirrhosis. Gene expression of the multifunctional cytokine, Oncostatin M (OSM), stimulates liver regeneration and adenoviral vector expressing OSM (AdOSM) allows a persistent expression of the gene. The aim of this study is to evaluate the benefits of the preoperative injection of AdOSM to the remnant lobes to regenerate the liver. Methods: A 70% partial hepatectomy was performed in dimethylnitrosamine-administrated cirrhotic rats with a preoperative injection of AdOSM, adenoviral vector carrying β-galactosidase (AdLacZ), or phosphate-buffered saline (PBS). The morphologic, histologic, and biochemical changes in the remnant liver and survival rates were then assessed. Results: Portal injection with clamping the portal branches of the resected lobes for 5 min made it possible to effectively transduce the adenoviral vector into the remnant lobes. The ratio of the remnant liver weight/body weight (%) was 2.3 ± 0.5 in the AdOSM group, 1.1 ± 0.3 in the AdLacZ group (p < 0.001), and 1.6 ± 0.4 in the PBS group (p = 0.02). The fibrous ratio (%) was 21.3 ± 4.6 in the AdOSM group and 35.2 ± 4.5 in the AdLacZ group on day 4 after hepatectomy and fibrous status was significantly decreased in the AdOSM group (p = 0.02). Serum hyaluronic acid which is the indicator of liver fibrosis was 215 ± 141 ng/mL in the AdOSM group and 1963 ± 1225 ng/mL in the AdLacZ group (p = 0.03). Conclusions: The OSM gene therapy may increase the possibility of hepatectomy in a cirrhotic liver by improving fibrosis, hepatic function, and hepatocyte regeneration.展开更多
AIM: To identify the key cytokines involved in hepatic differentiation of mouse bone marrow mesenchymal stem cells (mBM-MSCs) under liver-injury conditions. METHODS: Abdominal injection of CCl4 was adopted to duplicat...AIM: To identify the key cytokines involved in hepatic differentiation of mouse bone marrow mesenchymal stem cells (mBM-MSCs) under liver-injury conditions. METHODS: Abdominal injection of CCl4 was adopted to duplicate a mouse acute liver injury model. Global gene expression analysis was performed to evaluate the potential genes involved in hepatic commitment under liver-injury conditions. The cytokines involved in hepatic differentiation of mBM-MSCs was function-ally examined by depletion experiment using specifi c antibodies, followed by rescue experiment and direct inducing assay. The hepatic differentiation was characterized by the expression of hepatic lineage genes and proteins, as well as functional features. RESULTS: Cytokines potentially participating in hepatic fate commitment under liver-injury conditions were initially measured by microarray. Among the up-regulated genes determined, 18 cytokines known to closely relate to liver growth, repair and development, were selected for further identif ication. The f ibroblast growth factor-4 (FGF-4), hepatocyte growth factor (HGF) and oncostatin M (OSM) were fi nally found to be involved in hepatic differentiation of mBM-MSCs under liver-injury conditions. Hepatic differentiation could be dramatically decreased after removing FGF-4, HGF and OSM from the liver-injury conditioned medium, and could be rescued by supplementing these cytokines. The FGF-4, HGF and OSM play different roles in the hepatic differentiation of mBM-MSCs, in which FGF-4 and HGF are essential for the initiation of hepatic differentiation, while OSM is critical for the maturation of hepatocytes. CONCLUSION: FGF-4, HGF and OSM are the key cytokines involved in the liver-injury conditioned medium for the hepatic differentiation of mBM-MSCs.展开更多
文摘BACKGROUND Oncostatin M(OSM)is a pleiotropic cytokine which is implicated in the path-ogenesis of inflammatory bowel disease(IBD).AIM To evaluate the prognostic role of OSM in IBD patients.METHODS Literature search was conducted in electronic databases(Google Scholar,Embase,PubMed,Science Direct,Springer,and Wiley).Studies were selected if they reported prognostic information about OSM in IBD patients.Outcome data were synthesized,and meta-analyses were performed to estimate standardized mean differences(SMDs)in OSM levels between treatment responders and non-res-ponders and to seek overall correlations of OSM with other inflammatory bio-markers.RESULTS Sixteen studies(818 Crohn’s disease and 686 ulcerative colitis patients treated with anti-tumor necrosis factor-based therapies)were included.OSM levels were associated with IBD severity.A meta-analysis found significantly higher OSM levels in non-responders than in responders to therapy[SMD 0.80(0.33,1.27);P=0.001],in non-remitters than in remitters[SMD 0.75(95%CI:0.35 to 1.16);P<0.0001]and in patients with no mucosal healing than in those with mucosal heal-ing[SMD 0.63(0.30,0.95);P<0.0001].Area under receiver operator curve values showed considerable variability between studies but in general higher OSM levels were associated with poor prognosis.OSM had significant correlations with Simple Endoscopic Score of Crohn’s disease[r=0.47(95%CI:0.25 to 0.64);P<0.0001],Mayo Endoscopic Score[r=0.35(95%CI:0.28 to 0.41);P<0.0001],fecal calprotectin[r=0.19(95%CI:0.08 to 0.3);P=0.001],C-reactive protein[r=0.25(95%CI:0.11 to 0.39);P<0.0001],and platelet count[r=0.28(95%CI:0.17 to 0.39);P<0.0001].CONCLUSION OSM is a potential candidate for determining the severity of disease and predicting the outcomes of anti-tumor necrosis factor-based therapies in IBD patients.
文摘In the present study, FBL3 murine erythroleukemia cells were transfected with human OSM(hOSM) gene by recombinant adenovirus, then the immunological properties of hOSM genetransfected FBL3 cells(FBL3OSM+) were investigated. 4 hours after transfection with hOSM gene, hOSM could be detected in the supernatant of FBL3OSM+ cells and hOSM secretion peaked at 24 h. The proliferation of FBL3OSM+ cells was inhibited markedly. The clonal formation of FBL3OSM+ cells was suppressed more obviously in comparison with wildtype FBL3 cells when analysed in clonal argar culture. Flow cytometry analysis showed that FBL3OSM+ cells expressed higher levels of Fas protein, B7 and ICAM1 molecules.FBL3OSM+ cells also expressed higher level of MHC class I molecules(H2Kb) but remained unchanged in expression of MHC class II molecules (Ia). CD14, which is a specific marker of monocyte/macrophage and not expressed on the wildtype FBL3 cells, was also detected on the surface of FBL3OSM+ cells. The results suggested that OSM gene transfer could increase the immunogenicity of FBL3 cells and promote their differentiation into macrophagelike cells. The data outline a promising approach to OSM gene therapy of leukemia mediated by recombinant adenovirus.
文摘Aim 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）. Methodology 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）. Results 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,res-pectively） 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 （≈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. Conclusion 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 bio-marker in the periodontal disease.
文摘Purpose:Oncostatin M(OSM) is a cytokine released by macrophages and lymphocytesthat can function as a growth regulator. A current study shows that leukemia inhibitoryfactor (LIF), a homologue of OSM, can prevent photoreceptor cell death when expressedin the lens of transgenic mice. We determined the efforts of lens-specific overexpressionof OSM on the development of eye.Methods: A truncated mouse OSM cDNA ( ～ 660 bp) was linked to the αA-crytallinpromoter, and injected into single-cell embryos with microinjection. Then, transgenic micewere established. The mRNA expression of transgene OSM was detected by in situhybridization. Immunohistochemistry was used to detect the expression of syntaxin, glialfibrillary acidic protein (GFAP), synaptophysin in the retinas of transgenic mice.Results: At embryonic day (E 17.5), the expression of the syntaxin at the inner and midportion of the retinas of transgenic mice was much higher than that of the retinas ofnon-transgenic mice. The expression of GFAP was detected in the retinas of transgenicmice, while no expression in non-transgenic normal FVB(FVB/N) mice was detected inthis stage. At postnatal day one (P1), the expression of synaptophysin was detected inthe retinas of transgenic mice, but there was no such expression in FVB/N mice.Conclusions: Lens-specific overexpression of OSM induces premature differentiation ofamacrine cells, gial cells, and photoreceptors in vivo.
文摘Background/Aims: Liver resection represents the treatment of choice for hepatocellular carcinoma (HCC) arising in well-compensated cirrhosis. Gene expression of the multifunctional cytokine, Oncostatin M (OSM), stimulates liver regeneration and adenoviral vector expressing OSM (AdOSM) allows a persistent expression of the gene. The aim of this study is to evaluate the benefits of the preoperative injection of AdOSM to the remnant lobes to regenerate the liver. Methods: A 70% partial hepatectomy was performed in dimethylnitrosamine-administrated cirrhotic rats with a preoperative injection of AdOSM, adenoviral vector carrying β-galactosidase (AdLacZ), or phosphate-buffered saline (PBS). The morphologic, histologic, and biochemical changes in the remnant liver and survival rates were then assessed. Results: Portal injection with clamping the portal branches of the resected lobes for 5 min made it possible to effectively transduce the adenoviral vector into the remnant lobes. The ratio of the remnant liver weight/body weight (%) was 2.3 ± 0.5 in the AdOSM group, 1.1 ± 0.3 in the AdLacZ group (p < 0.001), and 1.6 ± 0.4 in the PBS group (p = 0.02). The fibrous ratio (%) was 21.3 ± 4.6 in the AdOSM group and 35.2 ± 4.5 in the AdLacZ group on day 4 after hepatectomy and fibrous status was significantly decreased in the AdOSM group (p = 0.02). Serum hyaluronic acid which is the indicator of liver fibrosis was 215 ± 141 ng/mL in the AdOSM group and 1963 ± 1225 ng/mL in the AdLacZ group (p = 0.03). Conclusions: The OSM gene therapy may increase the possibility of hepatectomy in a cirrhotic liver by improving fibrosis, hepatic function, and hepatocyte regeneration.
基金Supported by The Grant of Medicine and Health Key Projects of Zhejiang Province, Science and Technology Fund of Ministry of Health of the People’s Republic of China, No. WKJ2007-2-037Shaoxing Key Project for Science and Technology, No. 2007A23008the Natural Science Foundation of Zhejiang Province, China, No. Y2090337
文摘AIM: To identify the key cytokines involved in hepatic differentiation of mouse bone marrow mesenchymal stem cells (mBM-MSCs) under liver-injury conditions. METHODS: Abdominal injection of CCl4 was adopted to duplicate a mouse acute liver injury model. Global gene expression analysis was performed to evaluate the potential genes involved in hepatic commitment under liver-injury conditions. The cytokines involved in hepatic differentiation of mBM-MSCs was function-ally examined by depletion experiment using specifi c antibodies, followed by rescue experiment and direct inducing assay. The hepatic differentiation was characterized by the expression of hepatic lineage genes and proteins, as well as functional features. RESULTS: Cytokines potentially participating in hepatic fate commitment under liver-injury conditions were initially measured by microarray. Among the up-regulated genes determined, 18 cytokines known to closely relate to liver growth, repair and development, were selected for further identif ication. The f ibroblast growth factor-4 (FGF-4), hepatocyte growth factor (HGF) and oncostatin M (OSM) were fi nally found to be involved in hepatic differentiation of mBM-MSCs under liver-injury conditions. Hepatic differentiation could be dramatically decreased after removing FGF-4, HGF and OSM from the liver-injury conditioned medium, and could be rescued by supplementing these cytokines. The FGF-4, HGF and OSM play different roles in the hepatic differentiation of mBM-MSCs, in which FGF-4 and HGF are essential for the initiation of hepatic differentiation, while OSM is critical for the maturation of hepatocytes. CONCLUSION: FGF-4, HGF and OSM are the key cytokines involved in the liver-injury conditioned medium for the hepatic differentiation of mBM-MSCs.
