2007 Fiscal Year Final Research Report Summary
Arole of lipid mediators in chondrocyte
| Project/Area Number |
18591126
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
膠原病・アレルギー・感染症内科学
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| Research Institution | St.Marianna University School of Medicine |
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Principal Investigator |
MASUKO Kayo St.Marianna University School of Medicine, Department of Biochemistry, Assistant Professor (80288208)
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| Co-Investigator(Kenkyū-buntansha) |
KATO Tomohiro St. Marianna University School of Medicine, Department of Biochemistry, Professor (80233807)
NAKAMURA Hiroshi St. Marianna University School of Medicine, Department of Biochemistry, Docent (80227933)
YUDO Kazuo St. Marianna University School of Medicine, Institute Medical Science, Associate Professor (60272928)
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| Project Period (FY) |
2006 – 2007
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| Keywords | chondrocytes / osteoarthritis / rheumatoid arthritis / lipid mediator / sphingosine / S1P / proteoglycan / prostaglandin |
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| Research Abstract |
BACKGROUND: Sphingosine-1-phosphate (S1P), a downstream metabolite of ceramide, induces various bioactivities via two distinct pathways: as an intracellular second messenger or through receptor activation. The receptor for S1P (S1PR) is the family of Endothelial differentiation, sphingolipid G-protein-coupled receptor (EDG). We have here attempted to reveal the expression of EDG/S1PR in human articular chondrocytes (HAC), exploring the implications of S1P in cartilage degradation.
METHODS: Articular cartilage specimens were obtained from patients with rheumatoid arthritis (RA), osteoarthritis (OA) or traumatic fracture (representing normal chondrocytes) who underwent joint surgery. Isolated HAC were cultured in vitro by monolayer and stimulated with S1P in the presence or absence of inhibitors of signaling molecules. Stimulated cells and culture supernatants were collected and subjected to analyses using reverse transcription-polymerase chain reaction (MGR), Western blotting, and enzyme-linked immunosorbent assay (ELISA).
RESULTS: All of the tested HAC samples showed positive results in terms of EDG/S1PR expression in basal condition. When HAC was stimulated with S1P, a significant increase in prostaglandin (PG) E2 production was observed together with enhanced expression of cyclooxygenase (COX)-2. S1P stimulated extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) in HAC, and the PGE2 induction was abrogated by PD98059 and SB203580. Pertussis toxin inhibited the PGE2 induction from HAC by SW, suggesting an essential role for Gi protein. S1P also attenuated the expression of proteoglycan aggrecan, a component of cartilage matrix, in HAC at transcriptional
CONCLUSION : It was suggested that the S1P-induced PGE2 was at least in part involved in the aggrecan-suppressing effect of S1P, seeing as COX inhibitors attenuated the effect Accordingly, S1P might play an important role in cartilage degradation in arthritides.
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Research Products
(6 results)
