2007 Fiscal Year Final Research Report Summary
Analysi of the role of cartducin, a novel growth factor secreted from cartilage, on bone development
| Project/Area Number |
18592062
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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 |
Pathobiological dentistry/Dental radiology
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| Research Institution | Osaka University |
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Principal Investigator |
MAEDA Takashi Osaka University, Graduate school of dentistry, Assistant Professor (80324789)
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| Co-Investigator(Kenkyū-buntansha) |
FURUKAWA Souhei Osaka University, Graduate School of Dentistry, Professor (80173524)
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| Project Period (FY) |
2006 – 2007
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| Keywords | cartducin / growth factor / chondrocytes / chondroprogenitor cells / bone development / MAP kinase / PI3 kinase / endothelial cells |
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| Research Abstract |
Several growth factors and hormones regulate bone development. However, the molecular mechanisms are not thoroughly understood. We previously identified novel secretory protein from cartilage, and named it "cartducin". Our recent studies cleared that cartducin promotes proliferation of chondroprogenitor cells and chondrocytes. In this project, we first examined whether cartducin exists in serum and further investigated the intracellular signaling pathways stimulated by cartducin in mesenchymal chondroprogenitor cells. Our first analysis showed that cartducin was undetectable in mouse serum. Next, chondroprogenitor cells were stimulated with cartducin, and three major groups of mitogen-activated protein kinase (MAPK) pathways and the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway were examined. Cartducin activated extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt, and inhibition of these pathways by specific inhibitors blocked cartducin-induced DNA synthesis in chon
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droprogenitor cells. These data suggest that cartducin is a peripheral skeletal growth factor, and the proliferation of mesenchymal chondroprogenitor cells stimulated by cartducin is associated with activations of the ERK1/2 and PI3K/Akt signaling pathways. Furthermore, we hypothesized that cartducin is an anti-angiogenic factor because cartducin was expressed in avascular zone of cartilage. Our further analysis showed that cartducin promoted proliferation and migration of mouse endothelial cells. Stimulation of these cells by cartducin led to activation of ERK1/2 and p38 MAPK. Inhibition of ERK1/2 or p38 MAPK pathways by specific inhibitors blocked the cartducin-induced endothelial cell proliferation, and migration was blocked by inhibition of ERK1/2, but not p38 MAPK pathway. These results suggest that cartducin may be involved as a novel angiogenic factor in bone development. Taken together, our study indicates that cartducin plays important roles in regulating bone development as both a growth factor and an angiogenic factor through specific signaling pathways. Less
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