Korean J Anat.  2007 Dec;40(4):277-286.

Roles of Sphingosine-1 Phosaphate During Pathogenesis of Bone Destruction and Inflammation in Rheumatoid Arthritis Mice Model

Affiliations
  • 1Department of Anatomy, Wonkwang University School, Iksan, Chonbuk 570-749, Korea. jmoh@wku.ac.kr
  • 2Department of Neurosurgery, Wonkwang University School, Iksan, Chonbuk 570-749, Korea.
  • 3Department of Endocrinology, Wonkwang University School, Iksan, Chonbuk 570-749, Korea.
  • 4Department of Dermatology, Wonkwang University School, Iksan, Chonbuk 570-749, Korea.
  • 5Department of Obstetrics and Gynecology, Wonkwang University School, Iksan, Chonbuk 570-749, Korea.
  • 6Department of Orthopaedic Surgery, Wonkwang University School, Iksan, Chonbuk 570-749, Korea.
  • 7Department of Pathology, Wonkwang University School, Iksan, Chonbuk 570-749, Korea.
  • 8Department of Rheumatology Wonkwang University School of Medicine and Wonkwang Medical Science Institute, Iksan, Chonbuk 570-749, Korea.

Abstract

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-alpha, 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-alpha, 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

Keyword

S1P; Arthritis; TNF-alpha; IL-6; RANKL

MeSH Terms

Animals
Ankle Joint
Arthritis
Arthritis, Rheumatoid*
Bone Marrow Cells
Cell Proliferation
Collagen
Down-Regulation
Incidence
Inflammation*
Interleukin-6
Knee
Mice*
Osteoclasts
Peritoneal Cavity
Radiography
Sphingosine
Synovial Membrane
Tail
Tumor Necrosis Factor-alpha
Collagen
Interleukin-6
Sphingosine
Tumor Necrosis Factor-alpha
Full Text Links
  • KJA
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr