2004 Fiscal Year Final Research Report Summary
Mechanism of bone destruction due to Rheumatoid Arthritis in the fields of Osteoimmunology
| Project/Area Number |
15390637
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Orthodontic/Pediatric dentistry
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| Research Institution | The University of Tokushima |
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Principal Investigator |
MORIYAMA Keiji The University of Tokushima, Graduate School・Health Bioscience Center, Orthodontics and Dentofacial Orthopedics, Professor, 大学院・ヘルスバイオサイエンス研究部, 教授 (20262206)
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| Co-Investigator(Kenkyū-buntansha) |
HAYASHI Yoshio The University of Tokushima, Graduate School・Health Bioscience Center, Oral Pathology, Professor, 大学院・ヘルスバイオサイエンス研究部, 教授 (00127854)
OBA Yasuo The University of Tokushima, Graduate School・Health Bioscience Center, Orthodontics and Dentofacial Orthopedics, Associate professor, 大学院・ヘルスバイオサイエンス研究部, 助教授 (40294706)
HORIUCHI Shinya The University of Tokushima, Graduate School Health Bioscience Center, Orthodontics and Dentofacial Orthopedics, Assistant professor, 大学院・ヘルスバイオサイエンス研究部, 助手 (70263861)
KITASE Yukiho The University of Tokushima, Medical Dental Hospital, Orthodontics and Dentofacial Orthopedics, Assistant professor, 医学部・歯学部附属病院, 助手 (70363166)
TAKAHASHI Takumi The University of Tokushima, Graduate School・Health Bioscience Center, Orthodontics and Dentofacial Orthopedics, Assistant professor, 大学院・ヘルスバイオサイエンス研究部, 助手 (30363154)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Rheumatoid arthritis / Estrogen / RANKL / Bone destruction / MRL / lpr mice / Dendritic cell / Osteoclast |
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| Research Abstract |
Receptor activator of NF-kB ligand (RANKL) is known to be a key molecule of the osteoimmunology. The aim of this study was to analyze the effect of cell transfer of dedritic cells (DCs) stimulated with RANKL on the development of autoimmune arthropathy in MRL/lpr mice, and to evaluate the possible relationship between autoimmune responses and RANKL-mediated osteoclastogenesis. Matured bone marrow DC (BMDC) from MRL/lpr mice were stimulated with RANKL and chick type II collagen (CII), and were subcutaneously transferred one or three times into MRL/lpr mice. Acceleration of autoimmune arthritis with bone destruction was observed in RANKL/CII DC-transferred mice compared with the legions of non-transferred and non-pulsed DC-transferred, CII DC-transferred MRL/lpr mice. A significant shift to memory phenotypes of T cells was detected in RANKL/CII DC-transferred mice. It was shown that the expressions of MHC class II and RANKL-associated molecules including TRAF6, c-Fms, c-Fos, PU.1 c-Src, of the DCs from RANKL/CII DC-transferred mice were significantly upregulated. In addition, the bone marrow culture from RANKL/CII DC-transferred mice resulted in the increases of osteoclast formation and bone resorption, compared with those of non-DC-transferred mice. On the other hand, three times of transfer of RANKL/CII DC into MRL/lpr mice protected the development of autoimmune arthritis, and reduced the splenomegaly and lymphadenopathy through upregulation of Activation-induced cell death (AICD) of peripheral T cells. These results indicate that RANKL pathway plays a crucial role for immunomodulation of autoimmune arthropathy in a murine model for rheumatoid arthritis.
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