1. School of Medicine, China Medical University, Taichung, Taiwan
2. Department of Family Medicine, China Medical University Hsinchu Hospital, Hsinchu, Taiwan
3. Division of Immunology and Rheumatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
4. Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan
5. Department of Medical Education and Research, China Medical University Beigang Hospital, Yunlin, Taiwan
6. Department of Sports Medicine, College of Health Care, China Medical University, Taichung, Taiwan
7. Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan
8. Department of Orthopedic Surgery, China Medical University Beigang Hospital, Yunlin, Taiwan
9. Chinese Medicine Research Center, China Medical University, Taichung, Taiwan
10. Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan
# These authors contributed equally.
Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease, in which the immune system attacks joint tissue. Interleukin (IL)-6 is a key proinflammatory cytokine in RA progression. Sphingosine-1-phosphate (S1P), a platelet-derived lysophospholipid mediator, reportedly regulates osteoimmunology. Here, we examined the effects of S1P on IL-6 expression in osteoblasts. Our results and records from the Gene Expression Omnibus (GEO) database demonstrate higher levels of IL-6 in patients with RA compared with those with osteoarthritis. Stimulation of osteoblasts with S1P increased mRNA and protein expression of IL-6. PI3K, MEK, ERK and NF-κB inhibitors and their small interfering RNAs (siRNAs) reduced S1P-promoted IL-6 expression. S1P also facilitated PI3K, MEK/ERK and NF-κB signaling cascades. Our results indicate that S1P promotes the expression of IL-6 in osteoblasts via the PI3K, MEK/ERK and NF-κB signaling pathways.
Keywords: S1P, IL-6, Osteoblasts, Arthritis