Sphingosine kinase 2: a controversial role in arthritis.

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.