Background/Purpose:

Sphingolipids represent a major class of lipids that are ubiquitously expressed in eukaryotic cell membranes. Through the interaction with a family of five G-protein-coupled receptors (S1P1–5), sphingosine-1-phosphate (S1P) triggers diverse cellular responses, including cytoskeletal changes, proliferation, and migration. The importance of S1P in inflammation has been extensively demonstrated. Some reports have shown that elevated S1P level and S1P1, 3 expression are detected in RA synovium, and S1P signaling via S1P1 promotes synoviocyte proliferation. It is suggested that S1P is an important inflammatory mediator in the pathogenesis of arthiritis, but the role of S1P3 in the pathogenesis of arthiritis are poorly understood. Thus, we examine the role of S1P3 receptor signaling in the development of collagen-induced arthritis (CIA) in murine.

Methods:

Wild-type(WT) and S1P3-deficient(S1P3^-/-) mice backcrossed more than 9 generations to DBA/1J mice were immunized with bovine type II collagen (CII), and the severity of arthritis was assessed over time. The severity was assessed using an established semiquantitative scoring system of 0–4: 0=normal, 1=mild, 2=moderate, 3=severe and 4=most severe. The cumulative score for all four paws of each mouse (the maximum score is 16) was used as the arthritis score to represent overall disease severity and progression in an animal. Mice were sacrificed on the 42nd day and their paws were fixed in 4% buffered formaldehyde. Paraffin sections of paws stained with hematoxylin and eosin (H&E) were systematically scanned in a microscope and histopathological changes were scored based on cell infiltration, cartilage destruction and bone erosion parameters.

Results:

S1P3^-/- mice showed signiflcantIy lower arthritis severity score compared with WT mice (P < 0.05). Histopathological evaluation of paws obtained on day 42 showed marked reductions in synovial inflammation, cartilage destruction and bone erosion parameters in S1P3^-/-mice compared with WT mice (P < 0.05).

Conclusion:

These results indicate that S1P3 receptor signaling plays an important role in the development of murine collagen-induced arthritis model.This pathway could be a therapeutic target for rheumatoid arthritis, although further investigations are required to elucidate the mechanism via S1P3 receptor signaling.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-role-of-sphingosine-1-phosphate-receptor-3-signaling-in-murine-collagen-induced-arthiritis/