| Project/Area Number |
17591555
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
JINNO Tetsuya Tokyo Medical and Dental University, Graduate School, Lecturer (90343152)
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| Co-Investigator(Kenkyū-buntansha) |
SHINOMIYA Kenichi Tokyo Medical and Dental University, Graduate School, Professor (20111594)
TAKEDA Shu Tokyo Medical and Dental University, Graduate School, Associate Professor (30376727)
ASOU Yoshinori Tokyo Medical and Dental University, University Hospital Faculty of Medicine, Assistant Professor (50345279)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥300,000)
Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | osteoarthritis / Runx / transgenic mouse / 分子病態 |
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| Research Abstract |
We tried to address the molecular mechanism of the articular chondrocyte differentiation by using transgenic mice that display osteoarthritis. We overexpressed Runx1, Runx2 lacking the QA domain (ΔQA) or Runx3 in chondrocytes in vivo (α(1)II-Runx1, Runx2ΔQA or Runx3 mice, respectively). We analyzed these mice using histological and molecular methods. We also examined Runx expression in an experimental mouse model of mechanical stress-induced intervertebral disc (IVD) degeneration and in human patients with IVD degeneration. Runx1 expression was transiently observed in mesenchymal condensations, while Runx2 and Runx3 were robustly expressed in prehypertrophic chondrocytes. α(1)II-Runx2ΔQA and α(1)II-Runx3 mice developed ectopic mineralization of cartilage, lice in α(1)II-Runx2 mice, although α(1)II-Runx2ΔQA mice exhibited to a lesser extent. In contrast, α(1)II-Runx1 mice displayed no sign of ectopic mineralization. Surprisingly, α(1)II-Runx1 and α(1)II-Runx2 mice developed scoliosis due to IVD degeneration characterized by an accumulation of extracellular matrix and ectopic chondrocyte hypertrophy. During mouse embryogenesis, Runx2, but not Runx1 or Runx3, was expressed in the IVD. Moreover, in a mouse model, as in human patients with IVD degeneration, there was significant upregulation of Runx2 expression.
Collectively, Each Runx has a distinct yet overlapping role during chondrocyte differentiation. Runx2 contributes to the pathogenesis of IVD degeneration.
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