Grant-in-Aid for Scientific Research (B)
|Allocation Type||Single-year Grants|
Functional basic dentistry
|Research Institution||Showa University|
TAKAHASHI Naoyuki School of Dentistry, Showa University, Associate Professor, 歯学部, 助教授 (90119222)
KATAGIRI Takenobu School of Dentistry, Showa University, Lecturer, 歯学部, 講師 (80245802)
UDAGAWA Nobuyuki School of Dentistry, Showa University, Lecturer, 歯学部, 講師 (70245801)
SUDA Tatsuo School of Dentistry, Showa University, Professor, 歯学部, 教授 (90014034)
秋山 修一 昭和大学, 歯学部, 助手 (70276591)
自見 英治郎 昭和大学, 歯学部, 助手 (40276598)
|Project Period (FY)
1998 – 1999
Completed(Fiscal Year 1999)
|Budget Amount *help
¥12,900,000 (Direct Cost : ¥12,900,000)
Fiscal Year 1999 : ¥4,600,000 (Direct Cost : ¥4,600,000)
Fiscal Year 1998 : ¥8,300,000 (Direct Cost : ¥8,300,000)
|Keywords||osteoclast / osteoblast / osteoclast activiting factor / ODF / RANK / OPG / M-CSF / IL-1 / 1L-1 / 破骨細胞分化因子(ODF) / シグナル伝達 / osteoprotegerin(OPG) / osteoclastogenesis inhibitory factor(OCIF)|
We have investigated characteristics of osteoclast activating factor expressed by osteoblasts/stromal cells. The method for obtaining a large number of purified mononuclear and multinucleated osteoclasts was established in this study. Using the purification method, we analyzed the mechanism of activation of osteoclasts by osteoblasts/stromal cells.
(1) Osteoblasts enhanced survival of purified mononuclear and multinucleated osteoclasts, which resulted in formation of multinucleated osteoclasts. Osteoblasts also stimulated resorption pit-forming activity of osteoclasts through a mechanism involving cell-to-cell contact.
(2) M-CSF produced by osteoblasts also stimulated the survival of osteoclasts, but failed to stimulated pit-forming activity of osteoclasts.
(3) Osteoblasts obtained from M-CSF-deficient op/op mice stimulated not only survival of osteoclasts but also their pit-forming activity.
(4) Osteoblast-induced pit forming activity of osteoclasts was inhibited by osteoprotegerin (a dec
oy receptor for ODF) simultaneously added.
(5) Osteoclasts expressed high levels of IL-1 type 1 receptors and ODF receptors (RANK). Treatment of osteoclasts with IL-1 or ODF induced activation of NF-κB.
(6) IL-1 and ODF stimulated pit-forming activity of osteoclasts. IL-1 -induced osteoclast activation was inhibited by IL-1 receptor antagonist but not OPG, whereas ODF-induced osteoclast activation was specifically inhibited by OPG.
These results indicate that osteoclast activating factor expressed by osteoblasts/stromal cells is indeed ODF, the cDNA of which cloned in 1998. Recently, it was shown that TRAF6 knockout mice developed severe osteopetrosis. In TRAF6 knockout mice, many osteoclasts were found in bone but they failed to develop ruffled borders. As IL-1 receptors and RANK are shown to be interact with TRAF6, TRAF6-mediated signals appear to be important for IL-1 and RANK-induced activation of osteoclasts. It is also suggested that activation of NF-KB is important for induction of pit-forming activity of osteoclasts. Less