| Project/Area Number |
10470395
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Functional basic dentistry
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| Research Institution | Tokyo University of Pharmacy and Life Science |
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Principal Investigator |
MIYAURA Chisato Tokyo University of Pharmacy and Life Science, Department of Biochemistry, Associate Professor, 薬学部, 助教授 (20138382)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIMI Yoshiko The National Institute of Health and Nutrition, Department of Food Science, Senior Researcher, 食品科学部, 主任研究官 (50154159)
SUDA Tatsuo Showa University, Department of Biochemistry, Professor, 歯学部, 教授 (90014034)
ENDO Noriko Tokyo University of Pharmacy and Life Science, Department of Biochemistry, Research Associate, 薬学部, 助手 (80297605)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥13,100,000 (Direct Cost: ¥13,100,000)
Fiscal Year 1999: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1998: ¥9,700,000 (Direct Cost: ¥9,700,000)
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| Keywords | estrogen / osteoporosis / bone resorption / B lymphocyte / estrogebn receptor / 骨髄造血 |
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| Research Abstract |
We have reported that an estrogen deficiency caused by ovariectomy (OVX) selectively stimulates B-lymphopoiesis, resulting in a marked accumulation of pre-B cells in mouse bone marrow. Recently, osteoclast differentiation factor (ODF/RANKL/OPGL) has been cloned as a critical factor for osteoclast formation. In this study, we examined expression of ODF in trabecular bone and bone marrow B-cells in OVX mice. Female mice were sham operated or OVX. At 2-4 weeks, trabecular bone and bone marrow cells were collected from tibia for RT-PCR and western blot analyses to examine the expression of ODF. In OVX mice, bone mineral density was greatly reduced, and the number of B220-positive pre-B cells was greatly increased in bone marrow. OVX markedly induced expression of ODFmRNA and its protein in trabecular bone and bone marrow compared with sham mice. In immunostaining, expression of ODF could be detected in both osteoblasts in femoral trabecular bone and bone marrow B-lymphocytes. When B-cells
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were isolated from bone marrow uing B220-coated magnetic micro-beads, more than 98% of the isolated cells was B220-positive B-lymphocytes. The isolated B-cells constitutively expressed ODFmRNA, whereas expression of osteoprotegerin (OPG/OCIF)mRNA could not be detected in the B-cells. When the isolated B-cells were co-cultured with osteoblasts, the expression of ODF was greatly enhanced. To compare the level of expression of ODFmRNA in B-cells and osteoblasts, B-cells were separated from osteoblasts cell layer after the co-culture. The level of ODFmRNA in B-cells did not change before and after the co-culture. In contrast, osteoblasts co-cultured with B-cells greatly expressed ODFmRNA, suggesting that cell-to-cell interaction with B-cells stimulates expression of ODF in osteoblasts. These results suggest that both the increase in the number of B-lymphocytes, which constitutively express ODF, and the induction of ODF in osteoblasts by interaction with pre-B cells appear to be responsible for OVX-induced bone resorption with enhanced osteoclastogenesis. Less
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