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KMID : 0363720070400040277
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Korean Journal of Anatomy
2007 Volume.40 No. 4 p.277 ~ p.286
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Roles of Sphingosine-1 Phosaphate During Pathogenesis of Bone Destruction and Inflammation in Rheumatoid Arthritis Mice Model
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Kwak Han-Bok
Kwon Deok-Su
Jang Sung-Jo
Choi Eun-Young
Lee Eun-Gyeong
Park Byoung-Hyun
Kim Hyun-Dai
Seo Phil-Seung
Kim Jeong-Joong
Choi Min-Kyu
Cho Hae-Joong
Kim Jeong-Woo
Kim Hun-Soo
Lee Myeung-Su
Chun Churl-Hong
Oh Jae-Min
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Abstract
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Sphingosine 1-phosphate (S1P) is a bioactive lipid molecule that mediates cell proliferation, differentiation, migration, and angiogenesis in vivo. However, the roles of S1P on pathogenesis of arthritis have been not completely understood. This study was designed to determine the effects of S1P modulation on collageninduced arthritis (CIA) model. DBA/1J mice were injected with collagen into the tail for induction of CIA model. S1P was administered into the peritoneal cavity every other days from day 1 to day 42 after collagen injection. To determine the degree of damage in CIA, we examined macroscopic findings of CIA. The inflammation and bone destruction of CIA mice were evaluated by histo-patholigy and radiography (CT and microradiography). The expressions of TNF-α, IL-6, and RANKL which have important roles in pathogenesis of rheumatoid arthritis and bone destruction were observed by immuno-histochemical staining. After injection with collagen in the DBA/1J mice, CIA was induced by swelling in the knee and ankle joint. Administration of S1P suppressed damages and incidence of arthritis elicited by collagen. In histologic and radiographic studies, S1P strongly suppressed the infiltration of inflammatory cells, the swelling of synovial membrane, erosion, and the destruction of bone on CIA mice. Injection of S1P resulted in down-regulation of the expression of the pro-inflammatory and bone destruction mediators such as TNF-α, IL-6, and RANKL on CIA mice. Furthermore, S1P suppressed the differentiation of bone marrow cells into osteoclasts by RANKL. In conclusion, this study suggest that S1P has protective effects on inflammation and bone destruction during pathogenesis of CIA, which indicates S1P can be a new possible therapeutic strategy for rheumatoid arthritis
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KEYWORD
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S1P, Arthritis, TNF-α, IL-6, RANKL
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