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Published in: Rheumatology International 7/2014

01-07-2014 | Letter to the Editor

Sphingosine kinase 2: a controversial role in arthritis

Authors: Tao Xu, Lin Li, Cheng Huang, Yunyun Peng, Jun Li

Published in: Rheumatology International | Issue 7/2014

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Abstract

SphK2 is a nuclear protein that suppresses cell proliferation by inhibiting DNA synthesis, while also enhancing apoptosis in diverse cell types. ABC294640 (a selectively SphK2 inhibitor) attenuated the knee joint histological damage and pain associated with MIA-induced OA in rats. However, recent studies revealed that genetic inhibition of SphK2 did not significantly impact the severity or progression of inflammatory arthritis, while pharmacologic inhibition of SphK2 led to significantly more severe arthritis. Therefore, SphK2 plays a controversial role in arthritis.
Literature
1.
go back to reference Baker DA, Eudaly J, Smith CD, Obeid LM, Gilkeson GS (2012) Impact of sphingosine kinase 2 deficiency on the development of TNF-alpha-induced inflammatory arthritis. Rheumatol Int. doi:10.1007/s00296-012-2493-2 Baker DA, Eudaly J, Smith CD, Obeid LM, Gilkeson GS (2012) Impact of sphingosine kinase 2 deficiency on the development of TNF-alpha-induced inflammatory arthritis. Rheumatol Int. doi:10.​1007/​s00296-012-2493-2
2.
go back to reference Zhang L, Urtz N, Gaertner F, Legate KR, Petzold T, Lorenz M, Mazharian A, Watson SP, Massberg S (2013) Sphingosine kinase 2 (Sphk2) regulates platelet biogenesis by providing intracellular sphingosine 1-phosphate (S1P). Blood. doi:10.1182/blood-2012-12-473884 Zhang L, Urtz N, Gaertner F, Legate KR, Petzold T, Lorenz M, Mazharian A, Watson SP, Massberg S (2013) Sphingosine kinase 2 (Sphk2) regulates platelet biogenesis by providing intracellular sphingosine 1-phosphate (S1P). Blood. doi:10.​1182/​blood-2012-12-473884
3.
go back to reference Lai WQ, Irwan AW, Goh HH, Howe HS, Yu DT, Valle-Onate R, McInnes IB, Melendez AJ, Leung BP (2008) Anti-inflammatory effects of sphingosine kinase modulation in inflammatory arthritis. J Immunol 181(11):8010–8017PubMedCrossRef Lai WQ, Irwan AW, Goh HH, Howe HS, Yu DT, Valle-Onate R, McInnes IB, Melendez AJ, Leung BP (2008) Anti-inflammatory effects of sphingosine kinase modulation in inflammatory arthritis. J Immunol 181(11):8010–8017PubMedCrossRef
4.
go back to reference Kamada K, Arita N, Tsubaki T, Takubo N, Fujino T, Soga Y, Miyazaki T, Yamamoto H, Nose M (2009) Expression of sphingosine kinase 2 in synovial fibroblasts of rheumatoid arthritis contributing to apoptosis by a sphingosine analogue, FTY720. Pathol Int 59(6):382–389. doi:10.1111/j.1440-1827.2009.02381.x PubMedCrossRef Kamada K, Arita N, Tsubaki T, Takubo N, Fujino T, Soga Y, Miyazaki T, Yamamoto H, Nose M (2009) Expression of sphingosine kinase 2 in synovial fibroblasts of rheumatoid arthritis contributing to apoptosis by a sphingosine analogue, FTY720. Pathol Int 59(6):382–389. doi:10.​1111/​j.​1440-1827.​2009.​02381.​x PubMedCrossRef
6.
go back to reference Fitzpatrick LR, Green C, Frauenhoffer EE, French KJ, Zhuang Y, Maines LW, Upson JJ, Paul E, Donahue H, Mosher TJ, Smith CD (2011) Attenuation of arthritis in rodents by a novel orally-available inhibitor of sphingosine kinase. Inflammopharmacology 19(2):75–87. doi:10.1007/s10787-010-0060-6 PubMed Fitzpatrick LR, Green C, Frauenhoffer EE, French KJ, Zhuang Y, Maines LW, Upson JJ, Paul E, Donahue H, Mosher TJ, Smith CD (2011) Attenuation of arthritis in rodents by a novel orally-available inhibitor of sphingosine kinase. Inflammopharmacology 19(2):75–87. doi:10.​1007/​s10787-010-0060-6 PubMed
7.
go back to reference Fitzpatrick LR, Green C, Maines LW, Smith CD (2011) Experimental osteoarthritis in rats is attenuated by ABC294640, a selective inhibitor of sphingosine kinase-2. Pharmacology 87(3–4):135–143. doi:10.1159/000323911 PubMedCrossRef Fitzpatrick LR, Green C, Maines LW, Smith CD (2011) Experimental osteoarthritis in rats is attenuated by ABC294640, a selective inhibitor of sphingosine kinase-2. Pharmacology 87(3–4):135–143. doi:10.​1159/​000323911 PubMedCrossRef
Metadata
Title
Sphingosine kinase 2: a controversial role in arthritis
Authors
Tao Xu
Lin Li
Cheng Huang
Yunyun Peng
Jun Li
Publication date
01-07-2014
Publisher
Springer Berlin Heidelberg
Published in
Rheumatology International / Issue 7/2014
Print ISSN: 0172-8172
Electronic ISSN: 1437-160X
DOI
https://doi.org/10.1007/s00296-013-2831-z

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