| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Research Abstract |
Bone resorption by osteoclast involves initial stages of osteoclasts precursor cells migration, followed by differentiation into mature osteoclasts. Chemokine play essential roles in the chemotaxis to hematopoietic cells. In this grant, we established the effect of relationship chemokines to chemokine receptors on receptor activator of NF-kB ligand (RANKL)-stimulated osteoclast differentiation. CCL7 and CCL25 were induced from IL-1-and VitaminD3-stimulated ST2 cells, as osteoblastic cell line, simultaneously with RANKL production. On the other hand, CCR2 and CCR9, are well known CCL7 receptor and CCL25 receptor respectively, expressed in RAW264.7 cells, as osteoclast precursor cells. Neutralization of CCL7 and CCL25 antibody reduced RANKL-stimulated osteoclast differentiation by 50% approximately. Further, recombinant of CCL7 and CCL25 up-regulated the number of RANKL-induced multinuclear cells. Same results obtained from RANKL-stimulated bone marrow cells. Transwell migration activity in response to CCL7 was observed only when RANKL-treated RAW264.7 cells were used. CCL7 also significantly increased expression of RANK and NFATc1, but not Fra1 and AP1 in RANKL-treated RAW264.7 cells. Further, CCL7 significantly increased luciferase activity of NF-kB and NFAT reporter.
Taken together, these results suggest that CCL7-CCR2(or CCR1) may plays an important role in the RANKL-induced osteoclast differentiation, most likely osteoclast precursor cells migration.
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