1999 Fiscal Year Final Research Report Summary
Role of Cytokines Signaling in Osteoblastic Differentiation
| Project/Area Number |
10671739
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Osaka University |
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Principal Investigator |
NISHIMURA Riko Osaka University Faculty of Dentistry, Associate Professor, 歯学部, 助教授 (60294112)
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| Co-Investigator(Kenkyū-buntansha) |
YONEDA Toshiyuki Osaka University Faculty of Dentistry, Professor, 歯学部, 教授 (80142313)
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| Project Period (FY) |
1998 – 1999
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| Keywords | Osteoblast / IL-6 signaling / JAK kinases / STAT / MAP kinase / BMP / Smad / Cbfa1 |
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| Research Abstract |
1) Role of IL-6 in osteoblastic differentiation
We determined whether IL-6 plays a role in osteoblastogenesis using pluripotent mesenchymal cell line C3H10T1/2. IL-6 induced osteoblastic differentiation of C3H10T1/2 in the presence of sIL-6R, but not in the absence of it. One of IL-6 family cytokine, Oncostatin M also showed quite similar effects on C3H10T1/2. The data suggest that IL-6/sIL-6R is involved in osteoblastic differentiation of pluripotent mesenchymal cells.
2) Activation of IL-6 signaling during osteoblactic differentiation
To understand the molecular mechanisms by which IL-6 differentiates C3H10T1/2 into osteoblastic cells, we first determined the intracellular signaling cascade of IL-6 in C3H10T1/2. IL-6/sIL-6R induced tyrosine phosphorylation of gp130, JAK1, and JAK2. STAT1 and STAT3 were tyrosine-phosphorylated by IL-6/sIL-6R treatment, and translocated from cytoplasm into nucleus. IL-6/sIL-6R also activated MAP kinase. These results indicate that IL-6/sIL-6R concomitantl
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y activate JAK/STAT and MAP kinase pathway in C3H10T1/2.
3) Role of JAK/STAT and MAP kinase signaling in osteoblastic differentiation
In order to investigate the functional role of JAK/STAT signaling in osteoblastic differentiation, we examined the effects of dominant negative JAK1 (DN-JAK1) or JAK2 (DN-JAK2) on IL-6 induced osteoblastic differentiation. DN-JAK1 as well as DN-JAK2 blocked activation of JAK/STAT signaling. DN-JAK1 and DN-JAK2 also blocked IL-6 induced osteoblastic differentiation of C3H10T1/2. We, next, studied the role of MAP kinases in osteoblastic differentiation using dominant negative ras (DN-ras). DN-ras inhibited activation of MAP kinases. DN-ras partially inhibited activation of STAT and osteoblastic differentiation of C3H10T1/2. The data indicated that essential role of JAK/STAT signaling and the involvement of cross talk between JAK/STAT and MAP kinase signaling in osteoblastic differentiation induced by IL-6.
4) BMP2 signaling that regulates osteoblastic differentiation
We found BMP2 induced osteoblastic differentiation by inducing expression of Cbfa1 via activation of Smad signaling. Less
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