| Co-Investigator(Kenkyū-buntansha) |
MATSUURA Tetsuya The University of Tokushima, UNIVERSITY MEDICAL AND DENTAL HOSPITAL, ASSISTANT PROFESSOR (30359913)
NIKAWA Takeshi The University of Tokushima, GRADUATE SCHOOL, INSITUTE OF HEALTH BIOCIENCES, PROFESSOR (20263824)
SAIRYO Koichi The University of Tokushima, GRADUATE SCHOOL, INSITUTE OF HEALTH BIOCIENCES, LECTURER (10304528)
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| Budget Amount *help |
¥16,990,000 (Direct Cost: ¥15,700,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2007: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2006: ¥11,400,000 (Direct Cost: ¥11,400,000)
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| Research Abstract |
Distraction osteogenesis is a useful technique to study the response of bone to mechanical tension-stress in vivo. Using this technique, we here showed the unique response of bone to mechanical stress, especially the association between osteoactivin and MMP-3 expression. At 1 week after osteotomy of tibiae (the lag phase), mice were divided into two groups : the distraction osteogenesis group and non-distraction control group. In the first group, the tibiae were lengthened for 2 weeks (the distraction phase), followed by sustaining the length for 5 weeks (the consolidation phase). At 1 week after surgery, fibroblast-like cells (possible progenitors of osteoblasts or chondrocytes), which mainly expressed osteoactivin, were infiltrated into the osteotomy site. Interestingly, osteoactivin- and MMP-3-double positive fibroblast-like cells were accumulated in tibiae during the distraction phase. Consistent with immunohistochemical analysis, the levels of osteoactivin and MMP-3 transcripts in
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tibiae were significantly increased by osteotomy and distraction, respectively, in the distraction osteogenesis group, whereas no upregulated expression of MMP-3 was observed in the non-distraction group. To elucidate this difference in MMP-3 expression, we examined the shedding of osteoactivin during the distraction phase. Extracellular and intracellular fragments of osteoactivin were produced in distraction osteogenesis group, while they were hardly detected in the non-distraction group. These findings suggest that the shedding of osteoactivin is necessary for upregulation of MMP-3 expression in the lengthened segment. Finally, to address the role of osteoactivin-mediated MMP-3 expression in bone, osteoactivin-transgenic mice were subjected to this model. In osteoactivin-transgenic mice, bone resorption in the remodeling zone was significantly inhibited, compared with wild-type mice, whereas bone formation was not altered. We conclude that the shedding of osteoactivin functions as a mechanical tension-stress respondent inducer of MMP-3 for the fibroblast-like cells, and it mediates the inhibition of distracted callus resorption in the lengthened segment. Less
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