<scp>S1P</scp> facilitates <scp>IL</scp>‐1β production in osteoblasts via the <scp>JAK</scp> and <scp>STAT3</scp> signaling pathways

Abstract

Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease, in which the immune system attacks synovial joint tissues. Interleukin (IL)-1β is a critical proinflammatory cytokine in RA progression. Sphingosine-1-phosphate (S1P), a platelet-derived lysophospholipid mediator, reportedly regulates osteoimmunology. Here, we investigated how S1P mediates IL-1β expression in osteoblasts. Our analysis of records from the Gene Expression Omnibus (GEO) database demonstrate higher levels of IL-1β in patients with RA compared with those with osteoarthritis. Stimulation of osteoblasts with S1P concentration dependently increased mRNA and protein expression of IL-1β. Elevations in IL-1β mRNA expression induced by S1P were reduced by the small interfering RNA (siRNA) against the S1P₁ receptor. S1P also augmented JAK and STAT3 molecular cascades. We also found that JAK and STAT3 inhibitors and their siRNAs antagonized S1P-promoted IL-1β expression. Our results indicate that S1P promotes the expression of IL-1β in osteoblasts via the S1P₁ receptor and the JAK and STAT3 signaling pathways.