ArrayExpress Uploader0mouse over-expression over-expressionnormalnormal over-expressionnormalnormalnormalover-expressionnormalover-expressionnormalover-expression5968arrayexpress_sid6The study analyzes analyzes gene expression changes in the ankle joint in mouse TNFa overexpression models with or without sphingosine...E-GEOD-20152/profile/8773/arrayexpressuploader28ankleankle jointarthritisbonejointproteinDec.12, 2014Falsethe-role-of-sphk1-in-htnf-induced-inflammationE-GEOD-20152_A-AFFY-45The role of SphK1 in hTNFα induced inflammationNov.11, 2014The study analyzes analyzes gene expression changes in the ankle joint in mouse TNFa overexpression models with or without sphingosine kinase 1 activity. SphK1 is a sphingolipid enzyme that converts sphingosine to bioactive sphingosine-1-phosphate (S1P). Recent data suggest a potential relationship between SphK1 and TNFα and have implicated SphK1/S1P in the development and progression of inflammation. Here we further study the relationship of TNFα and SphK1 using an in vivo model. Transgenic hTNFα mice, which develop a spontaneous arthritis (limited to paws) at 20 weeks, were crossed with SphK1 activity null mice (SphK1-/-) to study the development of inflammatory arthritis in the functional absence of SphK1. Results show that hTNF/SphK1-/- have significantly less severity and progression of arthritis and bone erosions as measured through micro-CT images. Additionally, less COX-2 protein, mTNFα transcript levels and fewer Th 17 cells were detected in the joints of hTNF/SphK1-/- compared to hTNF/SphK1+/+ mice. Microarray analysis of the ankle joint showed that hTNF/SphK1-/- mice have increased transcript levels of IL-6 and SOCS3 compared to hTNF/SphK1+/+ mice. Finally, fewer mature osteoclasts were detected in the ankle joints of hTNF/SphK1-/- mice compared to hTNF/SphK1+/+ mice. These data show that SphK1 plays a role in hTNFα induced inflammatory arthritis, potentially through a novel pathway involving IL-6 and SOCS3. Two wild-type replicates; three replicates of human TNFa transgene overexpression and normal sphingosine kinase 1; three replicates of human TNFa transgene overexpression and sphingosine kinase 1 null.http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-20152http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-20152/samples/