| Co-Investigator(Kenkyū-buntansha) |
SUGIMOTO Itaru Keio University, Assistant, 医学部, 助手 (90255513)
IKEDA Toshiyuki Keio University, Assistant, 医学部, 助手 (80222892)
KOMUKAI Shigeyuki Keio University, Assistant, 医学部, 助手 (40234893)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1994: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Research Abstract |
(1) SD rats (22 weeks old) were divided into a sham group, an OVX group, and an OVX+E_2 group. After 3 months, the bone mineral densities (BMD) of the lumbar vertebrae (L_<3-5>) and the proximal end of the femur (F-P), metaphysis of the femur (F-M), and the distal end of the femur (F-D) were measured with DXA.In addition, the levels of osteocalcin (OC) in blood and deoxypyridinoline (D-Pyr) in urine were meaured before and after treatment. The BMDs of L_<3-5>, F-P,and F-D in the OVX group were significantly lower than those in the sham group, but there was no change in F-M.The BMDs of L_<3-5>, and F-D in the OVX+E_2 group were significantly higher than those in the OVX group, but there was no change in F-M.The %D-Py/Cr ratio, an indicator of bone resorption, was significantly higher in the OVX group than in the sham group and significantly lower in the OVX+E_2 group than in the OVX group. There was no significant change in the %OC,an index of osteogenesis, in any group. Thses findings
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indicate that OVX promotes bone resorption, leading to decreased BMD at sites rich in cancellous bone (L_<3-5>, F-D,and F-P) but no change at sites rich in cortical bone (F-M). E_2 replacement inhibits the OVX-induced increase in bone resorption ; the decreased BMD caused by OVX is supplemented primarily by cancellous bone. (2) 8-week-old, female ddy mice were allocated into three groups as described above. Samples of bone marrow cells were taken at selected intervals after operation and studied by flow cytometry with the use of monoclonal antibodies to cell-surface antigens. In addition, bone marrow cells and a bone stromal cell line were cultured together. Two weeks after OVX,a remarkable increase was noted in number of B-220-positive nucleated cells (pre-B cells) in the bone marrow. This specific increase in pre-B cells was improved to the sham level after E_2 replacment. In contrast to the effects of OVX,the administration of excess E_2 to normal mice resulted in a remarkable decrease in the number of bone marrow B cells. In co-culture systems, E_2 inhibited the proliferation and differentiation of B cells. These findings suggest that changes in myelopoiesis induced by extreme E deficiency altered bone metabolism, which may have led to decreased BMD. Less
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