| Project/Area Number |
12670002
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
General anatomy (including Histology/Embryology)
|
|---|
| Research Institution | Showa University (2001)
Tohoku University (2000) |
|---|
Principal Investigator |
NAKAMURA Masanori Showa University, Department of School of Dentistry, Professor, 歯学部, 教授 (50180394)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KONDO Shintaro Showa University Department of School of Dentistry, Lecturer, 歯学部, 講師 (60186848)
EGAWA Kaoru Showa University Department of School of Dentistry, Associate Professor, 歯学部, 助教授 (60119162)
曽我 浩之 東北大学, 大学院・医学系研究科, 助手 (20282121)
八木 秀樹 近畿大学, 薬学部, 助手 (40250740)
伊藤 恒敏 東北大学, 大学院・医学系研究科, 教授 (90004746)
|
|---|
| Project Period (FY) |
2000 – 2001
|
| Project Status |
Completed (Fiscal Year 2001)
|
| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥2,200,000 (Direct Cost: ¥2,200,000)
|
|---|
| Keywords | Rheumatoid Arthritis / Bone Destruction / Neutrophils / Bisphosphonate / Collagen-induced arthritis / MMP / Elastase / ビスフォスフォネト / 破骨細胞 / 造血 |
|---|
| Research Abstract |
In this study, we investigated the possibility whether neutrophils in rheumatoid arthritis could destruct calcified bone in vivo and in vitro. Aminobisphosphonate (ABP), an inhibitor of osteoclastic bone resorption, was used to inhibit osteoclast activity in collagen-induced arthritis (CIA). Severe bone destruction in CIA was observed in the CIA mice treated with ABP. In the areawhere bone destruction was detected, many neutrophils were aligned along the destructed bone surface. Some of neutrophils were ruptured and scattered intracellular granules on and in the destructed bone. Bone lining cells were no longer deteted in this region. Some osteoclasts were also detected in this region. However, these osteoclast detached from bone surface and had no ruffled borders and clear zones, which indicated that osteoclast had no capacity to resorb bone. Furthermore, no collagen fibers were detected in the destructed bone matrix. These results strongly suggeted the possibility that neutrophils directly destructed calcified bone. Therefore, we next cocultured neutrophils from rheumatoid arthritis patients and bone fragments and investigated the changes of bone matrix ay the ultrastructural level. Typical collagen fibers in the bone fragments cocultured with neutrophils were disappeared. Destruction of collagen fibers in this culture system was inhibited by the addition of the inhibitors of MMP or elastase. These results indicated that neutrophils destructed bone matrix by their intrinsic proteases such as MMP and elastase.
|
