| Project/Area Number |
10671382
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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 | Keio University |
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Principal Investigator |
CHIBA Kazuhiro Keio University, Orthopaedic Surgery, Assistant Professor, 医学部, 講師 (80179952)
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| Co-Investigator(Kenkyū-buntansha) |
IMABAYASHI Hideaki Keio University, Orthopaedic Surgery, Resident, 医学部, 助手 (40296629)
TSUJI Takashi Keio University, Orthopaedic Surgery, Resident, 医学部, 助手 (60296639)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2000: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1998: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | intervertebral disc / nucleus pulposus / annulus fibrosus / cell culture / extracellular matrix / proteoglycan / collagen / cytokine / 線維論 / マトリックスメタロプロテアーゼ(MMP) / 骨形成因子(BMP) |
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| Research Abstract |
Purposes of the current studies were to investigate metabolism of various extracellular matrix molecules of nucleus pulposus (NP) and annulus fibrosus (AF) cells cultured in alginate beads system and its changes after administrations of various various cytokines such as interleukin-1α (IL-1α).
Both NP and AF cells formed two different extracellular matrix pools, cell-associated (CM) and further removed (FRM) components, however, NP cells, have poor ability to retain matrix in CM.AF cells produced more collagen than NP cells. In NP, over 60% of radiolabelled proteoglycans already existed in FRM at initial time point, however less than 40% of that was in FRM of AF at the same time point. Turnover rates of radiolabelled proteoglycans of NP cells in two matrix pools were similar to that of chondrocytes. Radiolabelled proteoglycan in CM of both annulus fibrosus and nucleus pulposus turnover much faster than those in FRM (15 vs>80 days). Treatment with IL-1α caused a significant increase in the rate of proteoglycan turnover in the beads, especially in the CM, of both the NP and AF.
Intervertebral disc cells retain their phenotypical stability and keep producing their specific macromolecule matrix in alginate beads. Acceleration of the rate of PG turnover, particularly in the CM, caused by IL-1α was similar to the age-related changes observed in our previous studies. IL-1α or related substances may play significant role in normal age related processes of intervertebral disc. By identifying metabolic changes occurring in distinct matrix compartments, the alginate bead culture system appears suited to study the effects of cytokines on the metabolism of disc cells. This culture system has applicability to further study the effects of other cytokines and growth factors, the results of which should provide useful information to elucidate possible mechanisms of disc degeneration and may ultimately lead to prevention and reversion of such processes.
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