| Budget Amount *help |
¥3,890,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
Osteoclasts (OC) are bone resorbing multinucleated giant cells that are derived from hemopoietic precursors of the monocyte-macrophage lineage. Osteoclasts rapidly undergo apoptosis unless they are stimulated by exogenous mediators, including M-CSF, RANKL. We demonstrated that MIP-1 gamma (CCL9), one of the common chemokine, was stimulated mature osteoclast survival. Chemokines play an important role in immune and inflammatory responses by inducing migration and adhesion of leukocytes, and have also been reported to participate in regulation of several integrin. However, the effect of these integrins and chemokines as survival factor for mature osteoclast remain unclear.
In this study, we can get these results until now.
1. RANKL-induced mature osteoclast from mouse bone marrow and RAW264.7 cells also up-regulated the expression of integrin beta7 gene using Gene Array and RT-PCR.
2. IL-1 AND VtD3-stimulated ST2, mouse osteoblast cell line, expressed several chemokine gene such as CCL7, CCL9 and CCL25 using Gene Array and RT-PCR.
3. RAW264.7 cells expressed the several chemokine receptor genes such as CCR2 and CCR9 using RT-PCR.
4. CCL9 strongly related to survival of mature osteoclast.
5. The osteoclast differentiation was inhibited by anti-integrin a4 antibody and anti-integrin α4β7 antibody, but not anti-integrin β7 antibody and anti-integrin αE antibody.
These results suggest that relationship between chemokines and integrins, such as CCL7 (or CCL9) -CCR2 and CCL25-CCR9, participated osteoclast differentiation and osteoclast survival.
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