Mechanism of bone destruction and bone loss associated with rheumatoid arthritis and inhibition by cytokine-binding peptides
| Project/Area Number |
08670537
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
内科学一般
|
|---|
| Research Institution | St.Marianna University School of Medicine |
|---|
Principal Investigator |
SUZUKI Yasuo St.Marianna University School of Medicine, Associate Professor, 医学部, 助教授 (90129495)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
IDE Mikako St.Marianna University School of Medicine, Lecturer, 医学部, 助手 (80213023)
|
|---|
| Project Period (FY) |
1996 – 1997
|
| Project Status |
Completed (Fiscal Year 1997)
|
| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1996: ¥1,400,000 (Direct Cost: ¥1,400,000)
|
|---|
| Keywords | rheumatoid arthritis / bone loss / bone destruction / Interleukin-1 / IL-1 binding peptide / osteoclast / 滑膜細胞 / 腫瘍懐死因子(TNFa) / インターロイキン-1(IL-1) / 骨量減少 |
|---|
| Research Abstract |
Rheumatoid synovium produces proinflammatory cytokines, prostaglandins, and proteases and they play an important role in the pathogenesis of bone destruction and bone loss. To clarify the mechanism of bone loss associated with arthritis, we investigated osteogenic and bone resorptive potential of bone marrow in adjubant arthritis (AA) rats and the effect of cytokine binding peptide on bone metabolism and bone mass in these animals. Marrow from AIA rats grew fewer fibroblast colony forming units (FCFU). Formation of osteoclast-like cells and resorption pits on the ivory slices were increased in bone marrow cultures from AA rats. The inhibition study by anti-cytokine antibodies suggets that this uncoupled state of bone resorption-formation linkage is partly mediated through interleukin-1 and THFalpha. We recently synthesized the overlapping peptides from extracellular domain of the human type I IL-1 receptor and this peptide had an ability to bind IL-1, as well as inhibit the action of IL-1 both in vitro and in vivo (IL-1 binding peptide : IL-1BP). Treatment of AA by IL-1BP suppressed polyarthritis dose-dependently and ameriolated abnormal bone metabolism and bone loss.
These results sugget that IL-1BP may be a potential treatment for rheumatoid arthritis and its bone involvement.
Recent studies demonstrated that tartrate-resistant acid phopsphatase (TRAP)-positive multinucleated cells were found in the granulation tisssue obtained from rappidly progressive destructive coxoarthropaty or in the border between rheumatoid pannus and bone tissue. However, the role of these osteoclast-like cells on the bone destruction is still unclear. We developed the culture system that synovial cells obtained from rheumatoid arthritis patients defferentiated to multinucleated giant cells in vitro. These cells exhibited TRAP activity and resorb bones in vitro. This s may be an useful in vitro system to study the mechanism of bone destruction in rheumoid arthritis.
|
Report
(3 results)
Research Products
(17 results)
