1.Over-expression of extracellular superoxide dismutase in mouse synovial tissue attenuates the inflammatory arthritis.
Dong Hoon YU ; Jun Koo YI ; Hyung Soo YUH ; Seo jin PARK ; Hei Jung KIM ; Ki Beom BAE ; Young Rae JI ; Na Ri KIM ; Si Jun PARK ; Do Hyung KIM ; Sung Hyun KIM ; Myoung Ok KIM ; Jeong Woong LEE ; Zae Young RYOO
Experimental & Molecular Medicine 2012;44(9):529-535
Oxidative stress such as reactive oxygen species (ROS) within the inflamed joint have been indicated as being involved as inflammatory mediators in the induction of arthritis. Correlations between extracellular-superoxide dismutase (EC-SOD) and inflammatory arthritis have been shown in several animal models of RA. However, there is a question whether the over-expression of EC-SOD on arthritic joint also could suppress the progression of disease or not. In the present study, the effect on the synovial tissue of experimental arthritis was investigated using EC-SOD over-expressing transgenic mice. The over-expression of EC-SOD in joint tissue was confirmed by RT-PCR and immunohistochemistry. The degree of the inflammation in EC-SOD transgenic mice was suppressed in the collagen-induced arthritis model. In a cytokine assay, the production of pro-inflammatory cytokines such as, IL-1beta, TNFalpha, and matrix metalloproteinases (MMPs) was decreased in fibroblast-like synoviocyte (FLS) but not in peripheral blood. Histological examination also showed repressed cartilage destruction and bone in EC-SOD transgenic mice. In conclusion, these data suggest that the over-expression of EC-SOD in FLS contributes to the activation of FLS and protection from joint destruction by depressing the production of the pro-inflammatory cytokines and MMPs. These results provide EC-SOD transgenic mice with a useful animal model for inflammatory arthritis research.
Animals
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Arthritis, Experimental/blood/*enzymology/metabolism
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*Arthritis, Rheumatoid/enzymology/pathology
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Fibroblasts/metabolism
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Gene Expression Regulation
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Inflammation/pathology
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Interleukin-1beta/blood/metabolism
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Joints/enzymology/pathology
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Matrix Metalloproteinases/blood/metabolism
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Mice
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Mice, Transgenic
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Reactive Oxygen Species/metabolism
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*Superoxide Dismutase/genetics/metabolism
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Synovial Fluid/*enzymology
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Synovial Membrane/pathology
2.GLB1 gene mutation and clinical characteristics of a patient with mucopolysaccharidosis type IVB.
Hong-lin LEI ; Jun YE ; Wen-juan QIU ; Hui-wen ZHANG ; Lian-shu HAN ; Xue-fan GU
Chinese Journal of Pediatrics 2012;50(7):549-553
OBJECTIVETo report the results of clinical characteristics, enzyme activity determination and mutation analysis of GLB1 gene in a Chinese patient with mucopolysaccharidosis (MPS) type IVB (Morquio B disease).
METHODA 14-year-old Chinese boy with MPS type IVB was firstly diagnosed by blood leucocytes galactosamine-6-sulfate sulfatase (GALNS) and β-galactosidase (GLB1) determination, who was characterized by short stature, multiplex skeletal abnormalities, difficulty in walking. PCR-sequencing analysis was applied to detect the mutations in GLB1 of the patient.
RESULTThe patient was characterized by dwarfism, pectus carinatum, kyphosis, normal intelligence, and no neurologic damage of spasms, linguistic capacity and so on. The patient had normal GALNS enzyme activity and very low GLB1 enzyme activity [5.03 nmol/(h·mg) vs. normal value 118 - 413 nmol/(h·mg) ] in leukocytes. A compound heterozygous missense mutations c.442C > T(p.R148C)/c.1454A > G(p.Y485C) in GLB1 gene were detected in this patient. The mutation p.Y485C is a novel variant. With the method of gene analysis of new variant, the mutation p.Y485C was considered to be a pathogenic mutation.
CONCLUSIONThe MPS IVB patient showed severe multiple skeletal deformities, normal intelligence, no neurologic damage and very low GLB1 enzyme activity, who carries compound heterozygous mutations p.R148C/p.Y485C. The mutation p.Y485C in GLB1 gene may be a novel pathologic mutation of MPS type IVB.
Adolescent ; Amino Acid Sequence ; Asian Continental Ancestry Group ; genetics ; Chondroitinsulfatases ; genetics ; metabolism ; DNA Mutational Analysis ; Humans ; Joints ; pathology ; Male ; Molecular Sequence Data ; Mucopolysaccharidosis IV ; enzymology ; genetics ; pathology ; Mutation, Missense ; Pedigree ; Polymerase Chain Reaction ; Radiography ; Spine ; diagnostic imaging ; pathology ; beta-Galactosidase ; genetics ; metabolism