{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T01:21:13Z","timestamp":1791422473711,"version":"4.3.3"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2010,8,1]],"date-time":"2010-08-01T00:00:00Z","timestamp":1280620800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Sphingosine kinase 1 (SphK1) is an enzyme that converts sphingosine to bioactive sphingosine-1-phosphate. Recent in vitro data suggest a potential role of SphK1 in TNF-\u03b1\u2013mediated inflammation. Our aims in this study were to determine the in vivo significance of SphK1 in TNF-\u03b1\u2013mediated chronic inflammation and to define which pathogenic mechanisms induced by TNF-\u03b1 are SphK1 dependent. To pursue these aims, we studied the effect of SphK1 deficiency in an in vivo model of TNF-\u03b1\u2013induced chronic inflammatory arthritis. Transgenic hTNF-\u03b1 mice, which develop spontaneous inflammatory erosive arthritis beginning at 14\u201316 wk, were crossed with SphK1 null mice (SphK1\u2212\/\u2212), on the C57BL6 genetic background. Beginning at 4 mo of age, hTNF\/SphK1\u2212\/\u2212 mice had significantly less severe clinically evident paw swelling and deformity, less synovial and periarticular inflammation, and markedly decreased bone erosions as measured quantitatively through micro-CT images. Mechanistically, the mice lacking SphK1 had less articular cyclooxygenase 2 protein and fewer synovial Th17 cells than did hTNF\/SphK1+\/+ littermates. Microarray analysis and real-time RT-PCR of the ankle synovial tissue demonstrated that hTNF\/SphK1\u2212\/\u2212 mice had increased transcript levels of suppressor of cytokine signaling 3 compared with hTNF\/SphK1+\/+ mice, likely also contributing to the decreased inflammation in the SphK1-deficient mice. Finally, significantly fewer mature osteoclasts were detected in the ankle joints of hTNF\/SphK1\u2212\/\u2212 mice compared with hTNF\/SphK1+\/+ mice. These data indicate that SphK1 plays a key role in hTNF-\u03b1\u2013induced inflammatory arthritis via impacting synovial inflammation and osteoclast number.<\/jats:p>","DOI":"10.4049\/jimmunol.1000644","type":"journal-article","created":{"date-parts":[[2010,7,19]],"date-time":"2010-07-19T22:27:24Z","timestamp":1279578444000},"page":"2570-2579","source":"Crossref","is-referenced-by-count":86,"title":["Genetic Sphingosine Kinase 1 Deficiency Significantly Decreases Synovial Inflammation and Joint Erosions in Murine TNF-\u03b1\u2013Induced Arthritis"],"prefix":"10.1093","volume":"185","author":[{"given":"DeAnna A","family":"Baker","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Medical University of South Carolina , Charleston, SC 29425"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Barth","sequence":"additional","affiliation":[{"name":"Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina , Charleston, SC 29425"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond","family":"Chang","sequence":"additional","affiliation":[{"name":"Small Animal Imaging Core Facility, Department of Radiology and Radiological Sciences, Medical University of South Carolina , Charleston, SC 29425"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina M","family":"Obeid","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Medical University of South Carolina , Charleston, SC 29425"},{"name":"Department of Medicine, Medical University of South Carolina , Charleston, SC 29425"},{"name":"Department of Veterans Affairs, Ralph H. Johnson Veterans Affairs Medical Center , Charleston, SC 29401"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary S","family":"Gilkeson","sequence":"additional","affiliation":[{"name":"Department of Medicine, Medical University of South Carolina , Charleston, SC 29425"},{"name":"Department of Veterans Affairs, Ralph H. Johnson Veterans Affairs Medical Center , Charleston, SC 29401"},{"name":"Division of Rheumatology, Department of Medicine, Medical University of South Carolina , Charleston, SC 29425"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,8,15]]},"reference":[{"key":"2025032411462502900_r1","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1002\/art.1780310816","article-title":"Detection of tumor necrosis factor alpha but not tumor necrosis factor beta in rheumatoid arthritis synovial fluid and serum","volume":"31","author":"Saxne","year":"1988","journal-title":"Arthritis Rheum."},{"key":"2025032411462502900_r2","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1016\/S0140-6736(94)90628-9","article-title":"Randomised double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor alpha (cA2) versus placebo in rheumatoid arthritis","volume":"344","author":"Elliott","year":"1994","journal-title":"Lancet"},{"key":"2025032411462502900_r3","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/nrm2329","article-title":"Principles of bioactive lipid signalling: lessons from sphingolipids","volume":"9","author":"Hannun","year":"2008","journal-title":"Nat. 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