Mechanism of articular cartilage destruction in early-stage osteoarthritis and preclinical study on the development of diagnosis and treatment for early-stage osteoarthritis.
| Project/Area Number |
16H05454
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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 | Juntendo University |
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Principal Investigator |
Yasunori Okada 順天堂大学, 医学(系)研究科(研究院), 客員教授 (00115221)
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| Co-Investigator(Kenkyū-buntansha) |
デベガ スサーナ 順天堂大学, 医学部, 非常勤助教 (30623590)
平澤 恵理 順天堂大学, 医学(系)研究科(研究院), 教授 (50245718)
石島 旨章 順天堂大学, 医学(系)研究科(研究院), 准教授 (70365576)
チレッキ メフメット・ゼイネル 順天堂大学, 医学部, 博士研究員 (10827538)
下田 将之 慶應義塾大学, 医学部(信濃町), 講師 (70383734)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2018: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2017: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2016: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
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| Keywords | 変形性関節症 / 細胞外マトリックス / ヒアルロン酸分解 / アグリカン分解 / HYBID / ADAMTS4 / 早期変形性膝関節症 / 関節軟骨破壊 / 早期変形性関節症 / ヒアルロン酸代謝 / 骨・軟骨代謝 / 関節軟骨細胞 / 滑膜細胞 / ADAMTS / 関節軟骨破壊機構 / ADAMTS4/5 / 早期変形性関節症診断 |
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| Outline of Final Research Achievements |
We have carried out the studies on the destruction mechanisms of articular cartilage and development of diagnosis and treatments of early-stage knee osteoarthritis (OA), and obtained the following data: 1) HYBID (hyaluronan binding protein involved in hyaluronan depolymerization) knock-out mice show shortening of the long bones due to the inhibition of angiogenesis in the growth plate by accumulated high-molecular-weight hyaluronan. 2) HYBID is overexpressed in OA cartilage and synovial tissue, and involved in hyaluronan degradations in the cartilage and synovial fluid. 3) ADAMTS4 (a disintegrin and metalloproteinase with thrombospondin motifs-4) overexpressed by synovial tissue plays a central role in aggrecan degradation in OA cartilage. We have also developed human anti-ADAMTS4 neutralizing antibody. 4) Analysis of early-stage knee OA patients by T2 mapping MRI discloses a close relationship between osteophyte and changes in medial meniscus.
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| Academic Significance and Societal Importance of the Research Achievements |
OAは運動器疾患の中でも最も頻度が高く、健康寿命延伸阻害の主因であるが、その診断・治療法開発は遅れており、早期OAの病態解明や診断・治療法開発は喫緊の課題である。本研究で得られたOA関節軟骨におけるHYBIDの発現データや遺伝子欠損マウスの開発は、早期OAの進展機構の解明につながる可能性があり、ADAMTS4に対するヒト型中和抗体は、将来的に早期OA関節軟骨でのアグリカン分解抑制治療に応用することが期待される。早期膝OAのT2マッピングMRI解析により骨棘が早期より高頻度で観察され、骨棘が半月板の変性・破壊と関節軟骨破壊に関わることが示され、早期膝OAの有用な診断にとなる可能性が期待される。
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Report
(4 results)
Research Products
(24 results)
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[Journal Article] Hyaluronan-Binding Protein Involved in Hyaluronan Depolymerization Is Up-Regulated and Involved in Hyaluronan Degradation in Human Osteoarthritic Cartilage.2018
Author(s)
Shimizu H, Shimoda M, Mochizuki S, Miyamae Y, Abe H, Chijiiwa M, Yoshida H, Shiozawa J, Ishijima M, Kaneko K, Kanaji A, Nakamura M, Toyama Y, Okada Y.
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Journal Title
Am J Pathol.
Volume: 188
Issue: 9
Pages: 2109-2119
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Association of medial meniscal extrusion with medial tibial osteophyte distance detected by T2 mapping MRI in the patients with eraly-stage knee osteoarthritis.2017
Author(s)
Hada S., Ishijima M., Kaneko H., Kinoshita M., Liu L., Sadatusuki R., Futami I., Yusup A., Takamura T., Arita H., Shiozawa J., Aoki T., Takazawa Y., Ikeda H., Aoki S., Kurosawa H., Okada Y. and Kaneko K.
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Journal Title
Arthritis Res Ther
Volume: 19
Issue: 1
Pages: 201-201
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Osteoarthritis as a cause of locomotive syndrome: Its influence on functional mobility and activities of daily living.2016
Author(s)
Ishijima M., Kaneko H., Hada S., Kinoshita M., Sadatsuki R., Liu L., Shimura Y., Arita H., Shiozawa J., Yusup A., Futami I., Sakamoto Y., Ishibashi M., Machida S., Naito H., Arikawa-Hirasawa E., Hamada C., Saita Y., Takazawa Y., Ikeda H., Okada Y. and Kaneko K
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Journal Title
Clinic Rev Bone Miner Metab
Volume: 14
Issue: 2
Pages: 77-104
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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