| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1998: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
The formation of multinucleated giant cells (MGCs) from monocytes/macro-phages is controlled by various cytokines, the roles of which are not fully understood. Both interleukin (IL)-4 and 1α, 25(OH)ィイD22ィエD2 vitamin DィイD23ィエD2 (DィイD23ィエD2) are known to induce MGC formation from monocytes/macrophages. DィイD23ィエD2 is also known as a stimulator of osteoclast formation in the presence of stroma cells, and IL-4 as an inhibitor. Previously, we showed [hat IL-4-induced MGCs from monocytes/macrophages expressed tartrate resistant acid phosphatase (TRAP) activity and hydroxyapatite-resorptive activity in the presence of M-CSF without stroma cells, In this study, we examined the effects of DィイD23ィエD2 and/or IL-4 on MGC formation and the characteristics of these MGCs using a monoblastic cell line (UC3), to elucidate the involvement of these factors in osteoclast development without stroma cells. DィイD23ィエD2 -induced MGCs showed none of the markers of osteoclasts, such as TRAP activity, calcitonin r
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eceptor (cal-R) expression, hydroxyapatite-resorptive activity, and bone-resorptive activity. A low concentration of DィイD23ィエD2 synergistically stimulated IL-4-induced TRAP-positive MGC formation, where as a high concentration of DィイD23ィエD2 inhibited it. When IL-4 was added on day 7 of the 2-week culture with DィイD23ィエD2, TRAP positivity reached maximum. On the other hand, delayed addition of DィイD23ィエD2 on day 7 of culture did not increase the TRAP positivity. Although the fusion rate increased during the first week of the 2-week culture in the presence of DィイD23ィエD2, it increased further in the second week following the addition of IL-4 on day 7. Furthermore, IL-4-induced, or IL-4- and D3-induced MGCs differentiated into functional osteoclast with bone-resorptive activity following coculture with osteoblastic cells, whereas DィイD23ィエD2-induced MGCs did not acquire bone-resorptive activity even after coculture with osteoblastic cells in the presence of ィイD23ィエD2. These findings suggest that IL-4 initiates osteoclast development of UG3 cells, although stroma cells were necessary for development of functional osteoclasts. On the other hand, DィイD23ィエD2 had only a "supportive" effect on this differentiation, IL-4 and direct contact with stroma cells may regulate different stages in the multistep process of osteoclastogenesis of UG3 cells. Less
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