2010 Fiscal Year Final Research Report
Exploring molecular targets for the establishment of drug therapy for the ossification of the posterior longitudinal ligament of the spine
| Project/Area Number |
20590245
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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 |
General pharmacology
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| Research Institution | Hirosaki University |
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Principal Investigator |
FURUKAWA Kenichi Hirosaki University, 大学院・医学研究科, 准教授 (20165468)
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| Co-Investigator(Kenkyū-buntansha) |
SEYA Kazuhiko 弘前大学, 大学院・医学研究科, 助教 (40281919)
NUMASAWA Takuya 弘前大学, 大学院・医学研究科, 助教 (80396407)
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| Project Period (FY) |
2008 – 2010
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| Keywords | 異所性骨化 / 脊柱靱帯 / 機械的ストレス / 薬物治療 |
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| Research Abstract |
To verify the hypothesis that P2Y1 expression causes ossification in the spinal ligaments, we forced expression of P2Y1 in spinal ligament cells obtained from OPLL and non-OPLL patients. The expression of mRNA and protein was investigated by quantitative real-time polymerase chain reaction and immunofluorescence staining, respectively. After transfection, bone morphogenetic protein-2 (BMP-2) and Sox9 mRNA expression was significantly increased in spinal ligament cells derived from OPLL patients compared with cells from non-OPLL patients 2 days after P2Y1 transient transfection. Immunofluorescence analysis showed that BMP-2 and P2Y1 expression was increased in OPLL patients only, while Sox9 expression was increased in OPLL and non-OPLL patients. MRS2279, a selective P2Y1 antagonist, blocked the upregulation of Sox9 and BMP-2 after forced expression of P2Y1. Furthermore, 4 days after transient transfection of P2Y1, mineralization was observed only in spinal ligament cells from OPLL patients. These results suggest that P2Y1 expression plays an important role in ectopic bone formation in the spinal ligaments of OPLL patients and that a drug which modulates the P2Y1 function will be a potential candidate for the drug in the therapy of OPLL.
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[Journal Article] Genetic differences in the osteogenic differentiation potency according to the classification of ossification of the posterior longitudinal ligament of the cervical spine.2011
Author(s)
Kudo H, Yokoyama T, Ono A, Numasawa T, Wada K, Tanaka T, Asari T, Ueyama K, Motomura S, Toh S, Furukawa K-I
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Journal Title
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[Journal Article] A functional RNAi screen for runx2-regulated genes corresponding to ectopic bone formation in human spinal ligaments.2008
Author(s)
Kishiya M, Sawada T, Kanemaru K, Kudo H, Numasawa T, Yokoyama T, Motomura S, Ueyama K, Harata S, Toh S, Furukawa K-I
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Journal Title
Journal of Pharmacological Sciences 106
Pages: 404-414
Peer Reviewed
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[Presentation] Expression of GREM-1, one of the BMP antagonists, is significantly suppressed in the spinal ligament cells derived from patients with ossification of the posterior longitudinal ligament of the cervical spine.2011
Author(s)
Tanaka S, Asari T, Harada Y, Ono A, Numasawa T, Wada K, Yamasaki Y, Motomura S, Toh S, Furukawa K.-I.
Organizer
57th Annual Meeting of the Orthopaedic Research Society
Place of Presentation
Long Beach California, USA
Year and Date
20110113-20110116
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[Presentation] Genetic differences in osteogenic differentiation potency based on the classification for the ossification of the posterior longitudinal ligament of the cervical spine.2010
Author(s)
Kudo H, Furukawa K.-I., Ono A, Numasawa T, Wada K, Tanaka S, Asari T, Motomura S, Toh S
Organizer
56th Annual Meeting of the Orthopaedic Research Society
Place of Presentation
New Orleans, Lousiana, USA(Sympodium speaker)
Year and Date
20100306-20100309
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[Remarks] ホームページ等
