| Budget Amount *help |
¥5,700,000 (Direct Cost: ¥5,700,000)
Fiscal Year 1994: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1993: ¥4,300,000 (Direct Cost: ¥4,300,000)
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| Research Abstract |
1. We investigated the effects of lipopolysaccharide (LPS) on osteoclast-like cell formation induced by 1,25-dihydroxyvitamin D_3 in mouse bone marrow culture systems. LPS stimulated or inhibited the formation of osteoclast-like multinucleated cells (MNCs), in the presence or absence of dexamethasone, respectively. Such effects are presumably related to the amount of granulocyte-macrophage colony stimulating factor (GM-CSF) produced in the culture supernatant. 2. The effects of three LPS preparations from putative periodontopathic bacteria on osteoclastic differentiation were estimated using the same culture system as described above. We found those LPS as well as a synthetic lipid Asimilarly stimulated osteoclast-like cell formation, suggesting that a common structure of lipid A is likely to be involved in the stimulating activity. 3.We also found that dexamethasone, a synthetic glucocorticoid analog, directly affects bone marrow cells and enhances osteoclast generation by inhibiting
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the endogeneous production of GM-CSF,which may function as a negative regulator of osteoclast formation. 4.In the co-culture system of mouse bone marrow cells together with the mouse stromal cell line, ST 2, or with primary osteoblastic cells, basic fibroblast growth factor (bFGF) inhibited osteoclast-like cell formation. Our data suggested that bFGF inhibits the differentiation of progenitors to osteoclast-like cells and that stromal or osteoblastic cells but not osteoclast progenitors are target cells for bFGF to inhibit osteoclast-like cell formation. 5.Using the co-culture system shown above, we enriched tartrate-resistant acid phosphatase (TRAP) -positive MNCs by treating the cultures with dispase. In this system, macrophage-colony stimulating factor (M-CSF) and IL-1alpha were dffective in prolonging viability of TRAP-positive MNCs. 6.IL-1alpha was able to stimulate the osteoblast-like cell line, MC3T3-E1, to mobilize transcription factor NF-kappaB by electrophoretic mobility shift assays. With this method we are now investigating the effect of IL-1alpha on osteoclast-like cells enriched above for induction of activation of N1 kappaB. Less
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