| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2002: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
(1) Role of C/EBF beta in the differentiation of mesenchymal stem cells into osteoblasts and adipocytes
We found that C/EBP beta was expressed in mature osteoblasts as well as adipocytes, we, therefore, examined the role of C/EBP beta in osteoblastogenesis by overexpressing C/EBP beta using adenovirus technology. Overexpression of C/EBP beta able to induce the differentiation of mesenchymal stem cells into not only adipocytes but also osteoalasts. Furthermore, overexpression of C/EBP beta induced osteocalcin expression and transactivated osteocaicin promoter. The data indicated that C/EBP beta is an important transcription factor for osteoblast differentiation of mesenchymal cells.
(2) Cooperative role of C/EBP beta and Cbfal in osteoblast differentiation
We, next, evaluated the relationship between C/EBP beta and Cbfa1 that is a critical transcription factor in bone formation and osteoblastogenesis, and found that C/EBP beta physically associated with Cbfa1. More importantly, osteogenic action of Cbfa1 was further enhanced by overexpression of C/EBP beta, showing the important role of cooperation between C/EBP beta and Cbfa1 during osteoblast differentiation.
(3) Reciprocal role of C/EBP beta isoform, LIP, in osteoblastogenesis and adipogenesis
An isoform of C/EBP beta, LIP, was also expressed in mature osteoblasts, suggesting the role of LIP during osteoblastogenesis. Overexpression of LIP blocks the adipogenesis in a dominant-negative fashion, but exhibits osteogenic action as a co-factor for Cbfa1. Our data provide the new insight into the understanding the molecular mechanisms that determine the direction of mesenchymal stem cells in bone.
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