Comprehensive analysis of exosomes in cartilage and approach to the new strategy for osteoarthritis therapy
Project/Area Number |
17H04313
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Orthopaedic surgery
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Research Institution | Okayama University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
冨田 秀太 岡山大学, 医歯薬学総合研究科, 准教授 (10372111)
大月 孝志 岡山大学, 保健学研究科, 非常勤研究員 (10534802)
渡辺 彰吾 岡山大学, 保健学研究科, 准教授 (20548341)
西田 圭一郎 岡山大学, 医歯薬学総合研究科, 准教授 (80284058)
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Project Period (FY) |
2017-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2019: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2017: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
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Keywords | ADAMTS / 軟骨 / 遺伝子 / メタロプロテアーゼ |
Outline of Final Research Achievements |
Osteoarthritis (OA) is the most common bone and joint disease in the field of orthopedics. Exosomes contain various substances such as microRNA. We conducted an integrated analysis of cell-derived exosomes by two stress stimuli, mechanical stress and cytokine stimulation. A human cartilage-like cell line was used. We found that when microRNA-X was overexpressed in cartilage-like cells, it suppressed ADAMTS mRNA. Furthermore, we have found that microRNA-X effect on another unexpected molecule related to the extracellular matrix. Next, we found that one exosome surface molecule plays a very important role in the uptake of exosomes cells. Identification of this mechanism has a great impact on cell biology in understanding the signal transduction mechanism of exosomes, and can be expected to have a spillover effect. In order to solve this important problem, it is now necessary to develop new research.
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Academic Significance and Societal Importance of the Research Achievements |
あるエクソソーム表面分子が、軟骨様細胞へのエクソソーム取り込みに極めて重要な働きを担っていることを突きとめた。この現象は滑膜細胞では確認されず、軟骨様細胞特異的であると考えられた。 この発見は実はエクソソームの細胞に取り込まれるメカニズムが、細胞選択性や疾患特異性を表現している可能性を示唆する。このメカニズムの同定は、エクソソームの情報伝達機構を理解する上で、細胞生物学的にも大きなインパクトを与え、波及効果が期待できる。この重要課題を解決するために『エクソソームの表面膜成分』と『細胞側の取り込みタンパク』の2つを解明する、新たな研究を展開すべき状況となった。
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Report
(4 results)
Research Products
(68 results)
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[Journal Article] Mechanical strain attenuates cytokine-induced ADAMTS9 expression via transient receptor potential vanilloid type 12019
Author(s)
Ohtsuki T, Shinaoka A, Kumagishi-Shinaoka K, Asano K, Hatipoglu OF, Inagaki J, Takahashi K, Oohashi T, Nishida K, Naruse K, Hirohata S
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Journal Title
Experimental Cell Research.
Volume: 383
Issue: 2
Pages: 111556-111556
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] A High-Fat and High-Cholesterol Diet Induces Cardiac Fibrosis, Vascular Endothelial, and Left Ventricular Diastolic Dysfunction in SHRSP5/Dmcr Rats2018
Author(s)
Watanabe S, Kumazaki S, Kusunoki K, Inoue T, Maeda Y, Usui S, Shinohata R, Ohtsuki T, Hirohata S, Kusachi S, Kitamori K, Mori M, Yamori Y, Oka H.
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Journal Title
Journal of Atherosclerosis and Thrombosis
Volume: 25
Issue: 5
Pages: 439-453
DOI
NAID
ISSN
1340-3478, 1880-3873
Year and Date
2018-05-01
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] High molecular weight hyaluronan protects cartilage from degradation by inhibiting aggrecanase expression.2018
Author(s)
Ohtsuki T, Asano K, Inagaki J, Shinaoka A, Kumagishi-Shinaoka K, Cilek MZ, Hatipoglu OF, Oohashi T, Nishida K, Komatsubara I, Hirohata S.
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Journal Title
J Orthop Res
Volume: 36
Issue: 12
Pages: 3247-3255
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] ADAMTS1 null mice demonstrated omphalocele phenotypeAdamts1 was highly expressed in the ventral wall development2019
Author(s)
Omer Faruk Hatipoglu, Takashi Ohtsuki, Junko Inagaki, Courtney M Nelson, Timothy J Mead, Takuto Nishimura, Miho Tachiki, Kentaro Ikemura, Chang Lu, Yan Wanyu, Suneel S. Apte, Satoshi Hirohata
Organizer
ゴードンカンファレンス matrix metalloproteinase
Related Report
Int'l Joint Research
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[Presentation] IL-1 beta treatment up-regulated CD9 in exosome and chondrocyte2019
Author(s)
Wanyu Yan, Shintaro Kodama, Guole Liu, Takashi Ohtsuki, Omer Faruk Hatipoglu, Takuto Nishimura, Miho Tachiki, Junko Inagaki, Hiroshi Yamada, Takayuki Firumatsu, Keiichiro Nishida, Liankun Sun, Satoshi Hirohata
Organizer
第42回日本分子生物学会年会
Related Report
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[Presentation] Percutaneous coronary intervention for non-ST-segment elevation myocardial infarction in patient who underwent transcartheter aortic valve replacement.2019
Author(s)
Yasuhara K, Kagawa K, Kishinoue T, Mori1 H, Yoshino T, Yamaji T, Tanimoto M, Nakano Y, Hirohata S, Ueeda M, Ohnishi N, Takaishi A
Organizer
第28回 日本心血管インターベンション治療学会(CVIT)学術集会
Related Report
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[Presentation] Impact of Coronary Calcification findings with Non-triggered Computed Tomography for the Outcome of Perctaneous Coronary Interention in Patients with Acute Coronary Syndrome.2019
Author(s)
Yasuhara K, Hirohata S, Kishinoue T, Yoshino T, Mori H, Yamaji T, Tanimoto M, Kagawa K, Nakano Y, Ueeda M, Ohnishi N, Takaishi1 A
Organizer
第28回 日本心血管インターベンション治療学会(CVIT)学術集会
Related Report
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[Presentation] The Westerizaton of Life Style and Atherosclerosis in Japan ?The Balance of EPA and AA-2018
Author(s)
N. Matsuo, K. Hayashi, Y. Katou, M. Hasegawa, M. Tanimoto, T. Fujiwara, K. Kagawa, Y. Nakano, N. Oonishi, A. Takaishi, S. Hirohata, M. Ueeda.
Organizer
第86回欧州動脈硬化会議(EAS congress)
Related Report
Int'l Joint Research
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[Presentation] Supplementation of Omega-3 PUFAs could improve long term prognosis after PCI in patients without hyperlipidemia and diabetes.2018
Author(s)
N. Matsuo, K. Hayashi, Y. Katou, M. Hasegawa, M. Tanimoto, T.Fujiwara, K. Kagawa, Y. Nakano, N. Oonishi, A. Takaishi, S. Hirohata, M. Ueeda.
Organizer
第86回欧州動脈硬化会議(EAS congress)
Related Report
Int'l Joint Research
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[Presentation] Isolation and characterization of extracellular microvesicles in osteoarthritis2018
Author(s)
Liu G, Ohtsuki T, Shinaoka A, Komatsu K, Notsu Y, Hatipoglu OF, Nishimura T, Inagaki J, Yamada H, Nishida K, Sun L, Hirohata S.
Organizer
第41回日本分子生物学会年会
Related Report
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[Presentation] The Peculiar Factor Contributed to the Occurrence of Adverse Events Related to Use of Tolvaptan in Congestive Heart Failure Cases.2018
Author(s)
Yuichi Kato, Kazuna Hayashi, Misao Hasegawa, Naoaki Matsuo, Takashi Fujiwara, Masafumi Tanimoto, Kenzo Kagawa, Yukari Nakano, Nobuhiko Ohnishi, Atsushi Takaishi, Satoshi Hirohata, Masayuki Ueeda
Organizer
第82回日本循環器学会学術集会
Related Report
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[Presentation] A Trend of Increase in TG and Omega-3 PUFAs was Observed in All Age Groups of Patients with AMI.2018
Author(s)
Takashi Fujiwara, Yukari Nakano, Kazuna Hayashi, Yuichi Kato, Misao Hasegawa, Naoaki Matsuo, Masafumi Tanimoto, Kenzo Kagawa, Nobuhiko Ohnishi, Atsushi Takaishi, Satoshi Hirohata, Masayuki Ueeda.
Organizer
第82回日本循環器学会学術集会
Related Report
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[Presentation] The Clinical Pathway with Early Administration of Tolvaptan was Useful and Safe Even in Super-Elder Patients with Congestive Heart Failure.2018
Author(s)
Naoaki Matsuo, Kazuna Hayashi, Yuichi Kato, Misao Hasegawa, Takashi Fujiwara, Masafumi Tanimoto, Kenzo Kagawa, Nobuhiko Ohnishi, Satoshi Hirohata, Masayuki Ueeda, Atsushi Takaishi.
Organizer
第82回日本循環器学会学術集会
Related Report
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[Presentation] Supplementation of Omega-3 PUFAs to Patients with IHD Still Improved Their Long-term Prognosis in Strong Statin Era.2018
Author(s)
Naoaki Matsuo, Kazuna Hayashi, Yuichi Kato, Misao Hasegawa, Masafumi Tanimoto, Kenzo Kagawa, Yukari Nakano, Nobuhiko Ohnishi, Satoshi Hirohata, Masayuki Ueeda, Atsushi Takaishi.
Organizer
第82回日本循環器学会学術集会
Related Report
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[Presentation] Hospitalization Period could be Significantly Shortened by the Clinical Pathway with Early Administration of Tolvaptan in Congestive Heart Failure Cases.2018
Author(s)
Yuichi Kato, Kazuna Hayashi, Misao Hasegawa, Naoaki Matsuo, Masafumi Tanimoto, Takashi Fujiwara, Kenzo Kagawa, Yukari Nakano, Nobuhiko Ohnishi, Atsushi Takaishi, Satoshi Hirohata, Masayuki Ueeda
Organizer
第82回日本循環器学会学術集会
Related Report
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[Presentation] Inflammatory cytokine induced HYBID (HYALURONAN-BINDING PROTEIN INVOLVED IN HYALURONAN DEPOLYMERAZATION) -Expression mechanism-2017
Author(s)
Takashi Ohtsuki, Lyu Chen, Hiroyuki Yoshida, Akira Shinaoka, Kanae Kmagishi-Shinaoka, Mehmet Zeynel Cilek, Omer Faruk Hatipoglu, Junko Inagaki, Keiichiro Nishida, Yasunori Okada, Satoshi Hirohata
Organizer
HA2017
Related Report
Int'l Joint Research
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