| Project/Area Number |
11671466
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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 |
Orthopaedic surgery
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| Research Institution | Kurume University |
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Principal Investigator |
HIRAOKA Koji Kurume University, School of Medicine, assistant, 医学部, 助手 (10268914)
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| Co-Investigator(Kenkyū-buntansha) |
ZENMYO Michihisa Kurume University, School of Medicine, assistant, 医学部, 助手 (10289465)
KOMIYA Setsuro Kagoshima University, school of Medicine, Professor, 医学部, 教授 (30178371)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | p21 / chondrocyte / chondrosarcoma / differentiation / PTHrP / IGF-I |
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| Research Abstract |
The purpose of this study was to investigate the mechanism for regulating chondrocyte and chondrosarcoma cells differentiation. We focused on PTHrP and p21 which regulated the differentiation of chondrocytes and investigated how these factors interacted with each other in chondrocyte differentiation in the growth plate. PTHrP was strongly positive on immunostaining at the interface between the proliferating and the upper zone of the hypertrophic chondrocytes, where p21 was negative. On the other hand, p2l was positive in the lower zone of hypertrophic chondrocytes. Furthermore, PTHrP up-regulated the cell proliferation and down- regulated the expression of the p21 messengers in SW-1353 chondrosarcoma cells. These findings indicated that PTHrP might be a negative regulator for p21 in the differentiation of chondrocytes.
The histological grade of chondrosarcoma correlates well with their clinical behavior and length of survival. To assess the relationship of p21 and cell differentiation in chondrosarcoma, we examined p21 expression in 14 chondrosarcomas immunohistochemically and the induction of p21 by insulin-like growth factor-I (IGF-I) during cell differentiation in SW1353 chondrosarcoma cells. p21 immunoreactivity was seen in well differentiated chondrosarcoma cells, and was mutually exclusive with MIB1 reactivity in grade 1 chondrosarcomas. In vitro, proteoglycan synthesis of SW1353 cells was increased by IGF-I in a dose dependent manner. However, cell proliferation was not markedly stimulated. Overexpression of p21 mRNA and protein in SW1353 cells was induced by IGF-I 100ng/ml. Our results suggest that p21 expression is directly related to tumor differentiation, and is an important mediator of IGF-I in chondrosarcoma cells.
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