1996 Fiscal Year Final Research Report Summary
Analysis of gp130-induced signals which regulate osteclast formation and function
| Project/Area Number |
07457441
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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 |
Functional basic dentistry
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| Research Institution | Showa University |
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Principal Investigator |
TAKAHASHI Naoyuki School of Dentistry, Showa University, Associate Professor, 歯学部, 助教授 (90119222)
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| Co-Investigator(Kenkyū-buntansha) |
UDAGAWA Nobuyuki School of Dentistry, Showa University, Lecturer, 歯学部, 講師 (70245801)
MIYAURA Chisato School of Dentistry, Showa University, Lecturer, 歯学部, 講師 (20138382)
SUDA Tatsuo School of Dentistry, Showa University, Professor, 歯学部, 教授 (90014034)
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| Project Period (FY) |
1995 – 1996
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| Keywords | gp130 / IL-6 / IL-11 / IL-6 receptor / osteoclasts / osteoblasts / bone resorption / rheumatoid arthritis |
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| Research Abstract |
Existence of soluble interleukin-6 receptors (sIL-6R) triggers osteoclast formation induced by IL-6, a gp130-mediated cytokine, in co-culture of mouse osteoblastic cells and spleen cells. However, interleukin-11 (IL-11) and oncostatin M,which also use gp130 as a common signal transducer, stimulated osteoclast formation in the absence of respective soluble type receptors. We have studied how gp130-mediated signals regulate osteoclast formation and function. (1) RT-PCR analysis revered that osteoblastic cells expressed receptors for IL-11 but not for IL-6. Using transgenic mouse expressing IL-6 receptors (IL-6R), it was shown that the expression of IL-6R in osteoblastic cells is indispensable for osteoclast formation induced by IL-6 in co-cultures of mouse spleen cells and osteoblastic cells. (2) We examined the possible involvement of IL-6 together with sIL-6R in joinjt disruption of rheumatoid arthritis (RA) patients. Osteoclast-like multinucleated cells were found in synovium of RA patients. Synovial fluids from RA patients contained significantly elevated concentrations of both IL-6 and sIL-6R in comparison with those from osteoarthritis patients. (3) When osteoclasts were placed on dentine slices, they formed resorption pits within 24hr. Cytokines such as IL-6, IL-11 and oncostatin M did not influence pit forming activity of osteoclasts. In addition, osteoclast function was not affected by adding anti-mouse gp130 antibody to the pit formation assay. (4) Bone-resorbing factors such as 1alpha, 25(OH)_2D_3, PTH and PGE_2 stimulated production of IL-11 by osteoblastic cells. Anti-mouse gp130 antibody inhibited osteoclast formation induced by these bone-resorbing factors in co-culture of mouse osteoblastic cells and spleen cells. These results suggest that signals mediated by gp130 are involved in osteoclast formation but not in osteoclast function.
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