| Project/Area Number |
16390447
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Clinical Research Center for Rheumatology and Allergy, Sagamihara National Hospital, National Hospital Organization |
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Principal Investigator |
SUZUKI Ryuji Sagamihara National Hospital, National Hospital Organization, Clinical Research Center for Rheumatology and Allergy, Research Head, 室長 (70373470)
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| Co-Investigator(Kenkyū-buntansha) |
FUKUI Naoshi Sagamihara National Hospital, National Hospital Organization, Clinical Research Center for Rheumatology and Allergy, Research Head, 部長 (10251258)
OCHI Takahiro National Hospital, National Hospital Organization, Head of Hospital, 病院長 (80112035)
前田 朋子 塩野義製薬株式会社, 創薬研究所, 主任研究員 (90393024)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥13,900,000 (Direct Cost: ¥13,900,000)
Fiscal Year 2005: ¥6,100,000 (Direct Cost: ¥6,100,000)
Fiscal Year 2004: ¥7,800,000 (Direct Cost: ¥7,800,000)
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| Keywords | Rheumatoid arthritis / Osteoclast / Nurse cell / Inflammation / Gene-analysis / 骨破壊 / DNAチップ |
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| Research Abstract |
Objective : We have previously shown in vitro differentiation of monocytes into osteoclast-like multinucleated cells by granulocyte-macrophage colony-stimulating factor (GM-CSF), well-known as the potent inhibitor of osteoclastogenesis. We compared GM-CSF-induced multicleated cells with those induced by receptor activator of nuclear factor kappa B ligand (RANKL) to elucidate the attributes of osteoclast-like cells generated under the pathgenic condition of rheumatoid arthritis (RA).
Methods : The precursors were produced by the co-culture of monocytes with synovial nurse cells derived fro RA joints (RA-SNCs) and then subjected to the formation of multinucleated cells. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to measure the expression of matrix metalloproteinase (MMP)-12 and six osteoclast markers ; tartrate-resistant acid phosphatase (TRAP), crbonic anhydrase, cathepsin K, calcitonin receptor, integirin αV and MMP-9. TRAP and MMP-12 in RA joints specimen were evaluated histochemically.
Results : The mononuclear cells co-cultivated with RA-SNCs expressed ostoclast markers except for MMP-9, and maintained the ability of osteoclast-like cell formation induced by RANKL, RANKL-induced cells expressed MMP-9 as well as other ostoclast markers, but not MMP-12. On the other hand, by thestimulation of GM-CSF, the mononuclear cells also differentiated into osteoclast-like multinuleated cells expressing MMP-9 and MMP-12. Farthermore, the multinucleated cells producing MMP-12 were found in the erosive bone area of rheumatoid joints.
Conclusion : These findings suggest the presence of two distinct types of TRAP-positive multinucleated cells in RA joints. GM-CSF-induced cells, distinguishable from RANKL-induced cells by the expression of MMP-12, should be involved in the pathology of RA. The co-culture with RA-SNCs is very useful system to investigate mechanism of the differentiation of synovial macrophages and their roles in the pathogenesis of RA.
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