| Project/Area Number |
14570205
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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 |
Experimental pathology
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| Research Institution | Aichi Medical University |
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Principal Investigator |
SAGA Shinsuke Aichi Medical University, School of Medicine, Professor, 医学部, 教授 (40144141)
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| Co-Investigator(Kenkyū-buntansha) |
KOZAKI Kenichi Aichi Medical University, School of Medicine, Research assistant, 医学部, 助手 (50270715)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2002: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | caspin / PEDF / angiogenesis / apoptosis / cartilage / bone / ECM / 内軟骨骨化 / 膜性骨化 / EPC-1 |
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| Research Abstract |
In the endochondral ossification, chondrocytes in the growth plate change the phenotypes and form proliferative, mature and hypertrophic cartilage. Subsequently, hypertrophic cartilage is replaced by bone tissue through vascular invasion and resorption. However, the regulatory mechanism of vascular invasion in endochondral ossification is unknown. Cartilage is generally avascular and resistant to vascular invasion. However, hypertrophic cartilage is invaded by blood vessels during endochondral ossification. Vascular invasion (angiogenesis) is thought to be regulated by the balance of angiogenesis inducers and inhibitors. In this study we investigated the role of caspin/PEDF/EPC-1, which is a novel intrinsic anti-angiogenic factor, in the differentiation and the embryonic morphogenesis of cartilage tissue. The expression and distribution of caspin molecules in 15.5 day mouse embryos was analyzed by the immunohistochemical method and in situ hybridization. Both the immature mesenchymal cells and the mature cartilage cells expressed caspin mRNA or protein, and the expression was reduced and disappeared during transformation to the hypertrophic cartilage. Prominent deposition of caspin was detected in the region surrounding hypertrophic cartilage cells. It seems to behave as the inhibitor of vascular invasion into cartilage tissue. ATDC5 cells, mouse clonal chondrogenic cell line, which reflect the multistep process of chondrogenic differentiation from mesenchymal condensation to calcification in vitro. In this study, the expression of caspin and other factors during in vitro endochondral ossification with ATDC5 cells, was analyzed especially focusing on angiogenic and anti-angiogenic factors. Caspin was expressed in ATDC5 cells before the expression of type X collagen which is characterized in hypertrophic cartilage cells. Caspin was reduced and diminished in the differentiated ATDC5 cells.
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