2004 Fiscal Year Final Research Report Summary
The Role of Midkine in the Pathogenesis of Rheumatoid Arthritis
| Project/Area Number |
15590270
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Pathological medical chemistry
|
|---|
| Research Institution | Nagoya University |
|---|
Principal Investigator |
MURAMATSU Hisako Nagoya University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (50182134)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KADOMATSU Kenji Nagoya University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (80204519)
|
|---|
| Project Period (FY) |
2003 – 2004
|
| Keywords | midkine / rheumatoid arthritis / MK-deficient mouse / antibody-mediated arthritis / osteoclast / antisense oligo DNA / synovial membrane |
|---|
| Research Abstract |
Midkine(MK) is heparin-binding growth factor which promotes growth, survival and migration of various cells. The essential role of MK in migration of inflammatory cells has been shown using mice deficient in the MK gene. Here, we investigated the role of MK in the pathogenesis of rheumatoid arthritis(RA). MK levels in the sera and synovial fluid were increased in most cases of patients with RA, indicating a strong correlation between MK expression and RA. MK was expressed in macrophage-like cells and fibroblast-like cells in synovial membranes from the patients. In antibody-mediated arthritis, mice deficient in the MK gene seldom developed the disease, while most of the wild-type mice did. Administration of MK to the deficient mice increased the frequency of antibody-induced arthritis. Migration of inflammatory leukocytes to the synovial membranes in the disease models was suppressed in the MK-deficient mice. Furthermore, MK was found to promote the differentiation of osteoclasts from macrophages. In conclusion, MK participates in each of the two distinct phases of RA development, namely, migration of inflammatory leukocytes and osteoclast differentiation, and is a key molecule in the pathogenesis of RA.
|
Research Products
(12 results)
