2001 Fiscal Year Final Research Report Summary
The mechanism of osteoblastic differentiotion regulated by BMP-dependent transcription factors-A basic study directed to development of a treatment for senile osteoporosis
| Project/Area Number |
12671074
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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 |
Endocrinology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
NAKAYAMA Konosuke The University of Tokyo, Hospital, Assistant professor, 医学部・附属病院, 助手 (20322076)
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| Co-Investigator(Kenkyū-buntansha) |
FUKUMOTO Seiji The University of Tokyo, Hospital, Lecturer, 医学部・附属病院, 講師 (30202287)
TAKEUCHI Yasuhiro The University of Tokyo, Hospital, Assistant professor, 医学部・附属病院, 助手 (50202164)
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| Project Period (FY) |
2000 – 2001
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| Keywords | osteoporosis / osteoblast / bone formation / BMP / Smad / SIP-1 / myoblast / receptor tyrosine kinase |
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| Research Abstract |
1.The involvement of SIP-1 to osteoblastic and myoblastic differentiation.
Smad proteins play a critical role in intracellular signal transduction of BMP. SIP-1 is a transcription factor, which binds to Smad BMP-dependently and regulates the action of Smad. SIP-1 mRNA is induced by BMP in both osteoblastic MC3T3-E1 cells and myoblastic C2C12 cells, SIP-1 suppressed the responsiveness of Smad6 promoters in both cells, showing that SIP-1 inhibit BMP signal. SIP-1 also suppressed myoblastic differentiation, as shown by the promoter activity of a myoblastic marker, MCK.
2. The inhibition of BMP signal by receptor tyrosine kinase-mediated signals
Growth factors such as bFGF stimulate the proliferation of osteoblasts, while they suppress the osteoblastic differentiation. These growth factors are shown to suppress the BMP-responsiveness of Smad6 promoter, which is mediated by BMP-responsive element on Smad6 promoter and Smad protein, and by RTK-Ras-MEK-ERK pathway.
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