| Co-Investigator(Kenkyū-buntansha) |
MICHIGAMI Toshimi Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka Prefectural Hospital Oganizationn, Depatment of Environment Medicine, Director (00301804)
樋口 周久 大阪大学, 保健センター, 助手 (62347000)
村瀬 剛 大阪大学, 大学院医学系研究科, 助手 (50335361)
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| Budget Amount *help |
¥3,920,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Research Abstract |
Type XI collagen is a heterotrimer of three genetically distinct alpha chains, alpha 1(XI), alpha 2(XI) and alpha 3(XI), and is crucial for collagen fibril formation and skeletal morphogenesis. Type XI collagen is mostly found in cartilaginous tissues or in chondroblastic cells but its significant expression in osseous tissues or in osteoblastic cells has also been reported. Although transcriptional mechanisms for the alpha 2 type XI collagen gene(COL11A2) have been well documented in chondroblastic cells, osteoblastic cells have not been studied. In this study, we found that Saos-2 cells, a human osteosarcoma derived cell line, and primary cultures of normal human osteoblasts express COL11A2 mRNA under the control of Sp1 family of transcription factors, Sp1, Sp3 and Sp7/Osterix, through three functional Sp1 binding sites in the proximal promoter(JBMR 2006). Furthermore, we analyzed MG63 cells, a human osteosarcoma derived osteoblastic cell line, and found that Sp7/Osterix exclusively enhanced COL11A2 promoter activity in MG63 cells. Sp1 and Sp3 show ubiquitous expression pattern, and regulate a wide range of cellular function. In contrast, Sp7/Osterix shows bone tissue specific expression, and is essential for osteoblast differentiation and bone formation. Here we demonstrated that COL11A2 transcription is regulated by different contribution of the three Sp1 family members, Sp1, Sp3 and Sp7/Osterix, in various osteoblastic cells. In summary, the COL11A2 activation by Sp1 family members seems to be common in various osteoblastic cells. The reason for the different contribution of each Sp1 family member in various cells remains to be elucidated.
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